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Biomedical subjects

M Hanna

Publications and source records attributed to M Hanna.

At least 55 records · Page 3Linked to original sources
PubMed1995

Tandem autotransplantation for the treatment of metastatic breast cancer.

PURPOSE: To investigate the tolerability and impact on progression-free and overall survival of two consecutive cycles of high-dose chemotherapy (HDC) with autologous bone marrow transplantation (ABMT) in patients with previously untreated metastatic breast cancer. PATIENTS AND METHODS: Twenty-eight patients received conventional-dose induction therapy (ITx) followed by a planned two cycles of HDC with ABMT. Median age was 45 years (range, 34 to 60 years). Sites of disease were bone (seven patients), visceral (three), soft tissue (11), multiple (six), and CNS (one). The ITx regimens of cyclophosphamide, Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH), methotrexate, fluorouracil, prednisone, and tamoxifen (CAMFTP) (three patients); fluorouracil, doxorubicin, and cyclophosphamide (FAC; 11 patients); cyclophosphamide, methotrexate, and fluorouracil (CMF; four patients); or doxorubicin or mitoxantrone/cyclophosphamide (10 patients) were given to maximum response (three to five cycles). HDC was cyclophosphamide 6 g/m2, carboplatin 2 g/m2, and etoposide 625 mg/m2 with ABMT. RESULTS: Of 28 patients, 24 received two (86%) cycles of HDC. Four received only one cycle due to persistent toxicity from course 1 (one patient), no response to course 1 (two), and death on course 1 (one). Grade 3 to 4 nonhematologic toxicities included mucositis (in one or both cycles in 21 of 28 patients; 75%), diarrhea, nausea, and vomiting. Reversible peripheral neuropathy was seen in 15 of 28 patients and was severe in one. Documented infections were seen in 19 of 52 cycles. There was one transplant-related death. Six patients were converted from partial remission (PR) to complete remission (CR) with HDC; two of 24 patients (8%) were converted from PR to CR with the second cycle of HDC. Progression-free survival rate is nine of 28 patients (32%) with median follow-up of 23 months (range, 13 to 36+ months). Eighteen of 28 patients (64%) have progressed at 1 to 17 months from ABMT. CONCLUSION: Two cycles of HDC with ABMT was well tolerated with a high response rate in patients with metastatic breast cancer. The importance of the second cycle of HDC in this population is unclear.

Adult↗
PubMed1994

Suppression of mutations in the core of the Tetrahymena ribozyme by spermidine, ethanol and by substrate stabilization.

We have previously described a collection of mutations in conserved residues of the core of the Tetrahymena self-splicing intron. Most of these single base substitutions have less than 10% of the activity of their parental intron derivative [Couture, S., et al., (1990) J. Mol. Biol., 215, 345-358]. We examined the effect of two agents known to stabilize RNA structure, spermidine and ethanol, on the activity of many of these mutant RNAs. In the presence of either 5 mM spermidine or 20% ethanol most substitution mutations were partially or completely suppressed. These conditions also increased the temperature optima of both wild-type and mutant ribozymes. In addition, we find that mutations are also suppressed by a high concentration of GTP, a substrate in the reaction which is bound specifically by the intron. Thus we observe a general suppression of mutations in an RNA enzyme (ribozyme) by spermidine, ethanol and by substrate stabilization. These results are consistent with the idea that most mutations destabilize the folded structure of the ribozyme and can be suppressed by any of a variety of stabilizing influences.

Animals↗
PubMed1994

Evidence that the guanosine substrate of the Tetrahymena ribozyme is bound in the anti conformation and that N7 contributes to binding.

The group I self-splicing introns are RNA enzymes that catalyze phosphodiester-exchange reactions. These ribozymes have a highly specific binding site for guanosine, a substrate for the first self-splicing reaction (Bass & Cech, 1984). The binding site for guanosine has been localized to a specific region of the ribozyme (Michel et al., 1989), but the conformation of the bound guanosine substrate remains unknown. Most analogs of guanosine with substituents at C8 have a preference for the syn conformation; however, some C8-substituted analogs have the potential to form a hydrogen bond between the C8 substituent and the 5'-hydroxyl that would stabilize the anti conformation; we have found that analogs with the potential to form such a hydrogen bond are more active substrates than those that cannot form such a hydrogen bond. These observations led us to test 8-5'-O-cycloguanosine, which is locked in the anti conformation, and 8-(alpha-hydroxyisopropyl)guanosine, which is locked in the syn conformation; the former is active as a substrate, while the latter is inactive. These results strongly suggest that guanosine is bound to the ribozyme in the anti conformation and provide an additional constraint on structural models of this RNA enzyme. We have also examined a series of N7-substituted guanosine analogs; this position had previously been assumed to be unimportant for substrate binding since 7-methylguanosine is an excellent substrate. However, we have found that 7-deazaguanosine and 7-methyl-7-deazaguanosine are less active substrates than guanosine. We discuss several models for the role of N7 in guanosine binding.

Animals↗
PubMed1993

Efficacy of postoperative pain treatment regimens using both buprenorphine and papaveretum sequentially after abdominal hysterectomy.

We have undertaken a double-blind, controlled study to test the hypothesis that the efficacy of standard postoperative analgesia by papaveretum or buprenorphine is not compromised by previous or subsequent standard doses of the other agent. After total abdominal hysterectomy under a standardized general anaesthetic, 120 patients (four groups of 30) were allocated randomly to receive, on demand, a single i.v. dose of buprenorphine 0.15 mg or papaveretum 10 mg, followed sequentially by a single dose of i.m. buprenorphine 0.3 mg or papaveretum 20 mg. Three hours after the i.m. dose, all patients received sublingual buprenorphine 0.4 mg. Pain was scored using both a 10-cm horizontal visual analogue scale (VAS) and a nominal scale. Pain intensity differences and patient and nurse satisfaction with the regimens were recorded. Observations were continued for 8 h after operation. The efficacy of papaveretum or buprenorphine was not compromised by previous or subsequent standard doses of the other agent. All four treatment regimens were similarly well tolerated and gave acceptable analgesia in the immediate postoperative period.

Adolescent↗
PubMed1991

Malignant renal tumors in tuberous sclerosis.

Although the frequency of renal carcinoma in tuberous sclerosis is lower than that in von Hippel-Lindau syndrome, it occurs bilaterally in 43 percent of patients at a median age of twenty-eight years. Concomitant hamartomas and hyperplastic cystic components may confound the histologic diagnosis of renal carcinoma in tuberous sclerosis.

Adult↗
PubMed1990

Mutational analysis of conserved nucleotides in a self-splicing group I intron.

We have constructed all single base substitutions in almost all of the highly conserved residues of the Tetrahymena self-splicing intron. Mutation of highly conserved residues almost invariably leads to loss of enzymatic activity. In many cases, activity could be regained by making additional mutations that restored predicted base-pairings; these second site suppressors in general confirm the secondary structure derived from phylogenetic data. At several positions, our suppression data can be most readily explained by assuming non-Watson-Crick base-pairings. In addition to the requirements imposed by the secondary structure, the sequence of the intron is constrained by "negative interactions", the exclusion of particular nucleotide sequences that would form undesirable secondary structures. A comparison of genetic and phylogenetic data suggests sites that may be involved in tertiary structural interactions.

Animals↗
PubMed1989

The guanosine binding site of the Tetrahymena ribozyme.

The self-splicing Group I introns have a highly specific binding site for the substrate guanosine. Mutant versions of the Tetrahymena ribozyme have been used in combination with guanosine analogues to identify the nucleotide in the ribozyme that is primarily responsible for recognition of the guanine base.

Animals↗
PubMed1989

Bilateral duplex ectopic ureters terminating in the seminal vesicles: sonographic and CT diagnosis.

A 15-year-old boy presented with a short history of right-sided flank pain was found to have bilateral duplex renal systems with obstructed upper poles. Sonographic examination and contrast-enhanced delayed computed tomography (CT) performed at the conclusion of the excretory urography (EU) demonstrated termination of both obstructed ureters in the seminal vesicles. These noninvasive studies allowed accurate preoperative diagnosis of this abnormality.

Adolescent↗
PubMed1989

Comparison of intraperitoneal and subcutaneous insulin administration on lipids, apolipoproteins, fuel metabolites, and hormones in type I diabetes mellitus.

The relative biologic efficacy of intraperitoneal (IP) insulin administration over peripheral routes of insulin infusion for artificial delivery devices is still poorly documented. Thus, the effects of IP insulin administration have been compared with the effects of subcutaneous (SC) insulin administration upon circulating fuel metabolites, hormones and lipoproteins. In a longitudinal study, seven type I diabetic patients, aged 33 +/- 3 years, duration 16 +/- 4 years, were studied. SC intensive insulin therapy was used for 3 months, then insulin was infused IP via an implantable pump for 6 months with a similar good blood glucose control. Lipids including high density lipoprotein (HDL) cholesterol and low density lipoprotein (LDL) cholesterol, apolipoproteins A-I, A-II, and B were measured every 3 months. Although all values remained in the normal range, significant changes occurred in plasma triglycerides (63 +/- 9 SC v 88 +/- 12 mg/dL IP, P less than .05) and HDL-cholesterol (57 +/- 4 SC v 42 +/- 4 mg/dL IP, P less than .05) without concomitant changes in apolipoprotein levels. In another cross-sectional study, six of the patients consumed a standardized 400 kcal breakfast after 0.15 U/kg insulin. Eight SC insulin infused age-, glucose control- and weight-matched diabetic patients also underwent the same test using SC insulin. Six normal subjects consumed the same breakfast and served as controls. Plasma glucose, B-hydroxybutyrate, lactate, alanine, free fatty acids, free insulin and glucagon were measured for five hours after the meal. All measured parameters were comparable in both groups except free insulin and lactate.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗