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M M Goodman

Publications and source records attributed to M M Goodman.

At least 37 records · Page 2Linked to original sources
PubMed1996

Both total chain length and position of dimethyl-branching effect the myocardial uptake and retention of radioiodinated analogues of 15-(p-iodophenyl)-3,3-dimethylpentadecanoic acid (DMIPP).

Introduction of geminal dimethyl-branching into the 3-position of 15-(p-iodophenyl) pentadecanoic acid (IPPA) significantly delays myocardial clearance in rats and dogs following intravenous administration. Several new analogues of DMIPP have been synthesized and evaluated in fasted rats. The effects of both the position of dimethyl-branching and the total chain-length of 3, 3-dimethyl analogues on heart uptake and clearance kinetics have been studied. In the first series of compounds, two methyl groups were introduced into the 3-, 4-, 6-, or 9- position. Tissue distribution studies of the 15-(p-[I-125] iodophenyl)-analogues demonstrated that the position of dimethyl-branching is an important factor affecting both myocardial specificity and retention. The [I-125] labeled 3,3- and 4,4-DMIPP analogues showed higher myocardial uptake and faster blood clearance than the 6,6- and 9,9-DMIPP analogues [heart, % dose/gm heart: blood), 30 min: 3,3-DMIPP = 5.06 (12:1); 4,4-DMIPP = 8.03 (16.7: 1); 6,6-DMIPP = 2.26 (3.1:1); 9,9-DMIPP = 3.06 (2.77)]. In the second series, the effects of total fatty acid chain length were evaluated with 3,3-dimethyl-substituted analogues with C11, C12, C13, C14, C15, and C19 chain lengths. The C14 and C15 chain length analogues showed the best properties [global heart: blood ratios): 30 min: C11, 0.70 (0.82); C12, 1.25 (0.68); C13, 0.47 (0.90); C14, 1.63 (3.54); C15, 5.06 (12); C19. 1.29 (0.82). These detailed studies have demonstrated that both total chain length and the position of geminal dimethyl-branching are important structural parameters which affect myocardial specificity and retention of omega-(p-iodophenyl)-substituted fatty acid analogues and that 3,3-DMIPP and 4,4-DMIPP are the best candidates with optimal properties for further study.

Animals↗
PubMed1996

Evolution of anthocyanin biosynthesis in maize kernels: the role of regulatory and enzymatic loci.

Understanding which genes contribute to evolutionary change and the nature of the alterations in them are fundamental challenges in evolution. We analyzed regulatory and enzymatic genes in the maize anthocyanin pathway as related to the evolution of anthocyanin-pigmented kernels in maize from colorless kernels of its progenitor, teosinte. Genetic tests indicate that teosinte possesses functional alleles at all enzymatic loci. At two regulatory loci, most teosintes possess alleles that encode functional proteins, but ones that are not expressed during kernel development and not capable of activating anthocyanin biosynthesis there. We investigated nucleotide polymorphism at one of the regulatory loci, cl. Several observations suggest that cl has not evolved in a strictly neutral manner, including an exceptionally low level of polymorphism and a biased representation of haplotypes in maize. Curiously, sequence data show that most of our teosinte samples possess a promoter element necessary for the activation of the anthocyanin pathway during kernel development, although genetic tests indicate that teosinte cl alleles are not active during kernel development. Our analyses suggest that the evolution of the purple kernels resulted from changes in cis regulatory elements at regulatory loci and not changes in either regulatory protein function nor the enzymatic loci.

Alleles↗
PubMed1995

Comparative recombination distances among Zea mays L. inbreds, wide crosses and interspecific hybrids.

Recombination distances and linkage heterogeneity were compared among a wide range of maize inbreds, wide crosses and maize x teosinte hybrids. Twelve maize and four teosinte races were backcrossed to stocks fixed for rare marker alleles on chromosome arm 1L. Recombination fraction estimates were higher for exotic germplasm than for either U.S. maize or maize x teosinte crosses. Serrano, Tuxpeño and a US-adapted inbred line of tropical origin, NC300, exhibited enhanced recombination. Three of the four maize x teosinte hybrids had little or no recombination between two loci. The observed recombination "shrinkage" resulted from an apparent inversion in the vicinity of the Amp1 locus. Average recombination distances among common marker loci for composite maps were highly variable, even when map construction was restricted to maize germplasm of similar origins.

Cloning, Molecular↗
PubMed1995

Striatal dopamine transporter imaging in nonhuman primates with iodine-123-IPT SPECT.

UNLABELLED: The regional distribution, kinetics and pharmacological specificity of a new radioiodinated cocaine analog, N-((E)-3-iodopropen-2-yl)-2 beta-carbomethoxy-3 beta-(4-chlorophenyl) tropane ([123I]IPT) were examined in brain SPECT studies (n = 20) of nonhuman primates. METHODS: Radiolabeling and purification of the iododestannylated trialkyltin percursor yielded the tracer at greater than 90% radiochemical purity and high (> 20,000 Ci/mmole) specific activity. Cynomologous monkeys were injected with 7.2 +/- 1.3 mCi (mean +/- s.d.) of the tracer, and serial 10-min images were acquired (total scan time = 177 +/- 22 min). Images were reconstructed as transaxial slices (2 mm) using restorative techniques (Wiener prefiltering). RESULTS: Radioactivity concentrated quickly in striatal regions (time of peak = 25 +/- 13 min) and cleared gradually thereafter (8.8 +/- 4.6% hr). Striatal-to-cerebellar ratios of 2.6 +/- 1.5 (n = 19), 6.7 +/- 3.2 (n = 20), 15.1 +/- 10.7 (n = 10) and 22.8 +/- 11.0 (n = 9) were observed at the time of peak and at 1, 2 and 3 hr p.i., respectively. In contrast, extrastriatal activity peaked earlier and at lower levels, cleared more rapidly and resembled cerebellar time-activity curves. Displacing doses of nonspecific antagonists of monoamine transporters (mazindol and beta-CIT) showed that 95% of specific [123I]IPT binding was reversible, while selective antagonists (e.g., paroxetine, nisoxetine and GBR 12909) demonstrated that striatal activity was specifically associated with dopamine transporters. CONCLUSION: These results indicate that [123I]IPT is a useful radioligand for in vivo SPECT imaging of striatal dopamine transporters.

Animals↗
PubMed1994

Synthesis and characterization of radioiodinated N-(3-iodopropen-1-yl)-2 beta-carbomethoxy-3 beta-(4-chlorophenyl)tropanes: potential dopamine reuptake site imaging agents.

Methods have been developed for the preparation of radioiodinated N-substituted 2 beta-carbomethoxy-3 beta-(4-chlorophenyl)tropanes. The syntheses, physical properties, radiolabeling, and characterization of the pharmacological properties of N-(3(Z)-iodopropen-1-yl)-2 beta-carbomethoxy-3 beta-(4-chlorophenyl)tropane (12) and N-(3(E)-iodopropen-1-yl)-2 beta-carbomethoxy-3 beta-(4-chlorophenyl)tropane (13) are described. 2 beta-Carbomethoxy-3 beta-(p-substituted-phenyl)tropanes are potent ligands for the dopamine transporter. The radioiodinated derivatives are of interest because of the high uptake and prolonged striatal retention that may result from specific binding to low-capacity, high-affinity, dopamine reuptake sites. Radioiodine was introduced into the 3Z and 3E-position of N-(3-iodopropen-1-yl)-2 beta-carbomethoxy-3 beta-(4-chlorophenyl)tropane by iododemetalation of the corresponding 3-(tri-n-butylstannyl) derivatives. Competition binding data of various dopamine reuptake ligands with rat striatal tissue preparation for either [125I]-12 or [125I]-13 exhibited the following order of potency: E-13 > Z-12 > GBR 12909 >> mazindol >>> (-)-cocaine. Tissue distribution studies in rats showed that the E-13 was the best analogue. E-13 showed high striatal uptake (60 min, 1.23% dose/g; 120 min, 0.61% dose/g) and high striatal to cerebellum ratios (60 min, 15.9/1; 120 min, 16.5/1). These studies indicate that iodine-123-labeled E-13 is a potentially useful agent for imaging the dopamine reuptake sites by single-photon-emission computerized tomography.

Animals↗
PubMed1994

A controlled trial of topical propylthiouracil in the treatment of patients with psoriasis.

BACKGROUND: Propylthiouracil (PTU, 6-n-propyl 2-thiouracil) is an antithyroid thioureylene, which, in addition to its ability to decrease thyroid hormone synthesis, also has immune modulatory and free radical scavenging abilities. We have previously shown that oral PTU and another antithyroid thioureylene are effective in the treatment of plaque psoriasis. OBJECTIVE: The current study was performed to determine the efficacy of topical PTU in psoriasis. METHODS: Topical PTU and placebo were administered, in a double-blind fashion, three times daily for 4 to 8 weeks to nine volunteers with long-standing plaque psoriasis. The patients had biopsy specimens of their lesions taken at the start and end of the study. Clinical response was monitored with a scoring system based on scale, erythema, and thickness of the plaques. Complete blood cell count and thyroid function studies were obtained in each patient at the beginning and at 2-week intervals thereafter until completion of the study. RESULTS: Topically applied PTU produced significant clearing of the lesions (clinical scores 8.0 +/- 0.6 vs 3.7 +/- 0.3, p < 0.0001 at 4 weeks, and 4.0 +/- 0.6, p < 0.02 at 8 weeks); two patients demonstrated nearly complete clearing. Placebo-treated and untreated "control" areas showed no significant change during the study. None of the subjects had hypothyroidism or cytopenia. CONCLUSION: Topical applied PTU is effective in the treatment of patients with stable plaque psoriasis and has low toxicity.

Administration, Topical↗
PubMed1994

Comparison of the argon tunable dye laser with the flashlamp pulsed dye laser in treatment of facial telangiectasia.

BACKGROUND: A prospective, side-by-side comparison study of the argon tunable dye laser (ATDL) and the flashlamp pulsed dye laser (FPDL) for the treatment of solar-induced telangiectasia was carried out in 14 patients with symmetrical bilateral cheek telangiectasias. OBJECTIVE: The objective was to compare the efficacy of treatment by the two lasers. METHODS: Patients were treated and examined at weeks 2, 4, and 6. Evaluation was done by direct observation and questionnaire, as well as by photographic slides projected to an impartial panel. RESULTS: Final evaluation at week 6 showed 11 of 14 patients with excellent results at sites treated with the FPDL, compared with four of 14 with the ATDL. However, only six of 13 patients preferred the FPDL, due to the purpura and postinflammatory hyerpigmentation. CONCLUSION: We conclude that the objective final results favor the FPDL over the ATDL for treatment of facial telangiectasia, but that the ATDL is still an important option for patient acceptance.

Adult↗
PubMed1993

Comparison of the flashlamp pulsed dye laser with the argon tunable dye laser with robotized handpiece for facial telangiectasia.

This prospective study compares the efficacy, side effects, and patient acceptance of the flashlamp pulsed dye laser (FPDL) with the argon tunable dye laser with robotized handpiece (ATDL/H) for facial telangiectasias. Seventeen adult patients with bilaterally symmetric facial telangiectasias were enrolled. The right cheek on each patient was treated in one session with the FPDL at a fluence of 6.0-6.75 J/cm2 and a spot size of 5 mm. The left cheek was treated at the same session with the ATDL/H at a power of 1 W, a fluence of 26-27 J/cm2, and a hexagonal treatment area of 13 mm (127 individual 1 mm spots grouped mechanically by the handpiece). Patients were evaluated subjectively and by the investigators at 2, 4, and 6 weeks for blistering, swelling, bruising, changes in pigment, scarring, overall efficacy, and patient preference. Average treatment times were 5.4 minutes for FPDL and 9.4 minutes for ATDL/H. Blistering, crusting, and discomfort were completely resolved on both sides by week 2 in all patients. Bruising occurred in all patients with FPDL but had resolved in 62.5% of patients at 2 weeks and 100% at 4 weeks. There was no bruising with ATDL/H. Postinflammatory hyperpigmentation was much more prominent with FPDL but had resolved in 88% of cases by week 6. As rated by the investigators 100% of the FPDL treated areas showed excellent clearing of telangiectasias, compared with 47% of ATDL/H treated areas.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Propylthiouracil in psoriasis: results of an open trial.

BACKGROUND: Propylthiouracil (PTU) is an antithyroid thioureylene that has immune modulatory and free radical scavenging abilities. In view of the immunomodulatory effects of PTU, we decided to study the therapeutic response of patients with psoriasis to oral PTU. OBJECTIVE: Our purpose was to study the effect of oral PTU in patients with stable plaque psoriasis. METHODS: Oral PTU, 100 mg, was administered every 8 hours for 8 weeks to 10 patients with long-standing psoriasis. Skin biopsy specimens were taken from the lesions before and at the end of the study. Clinical response was monitored with the Psoriasis Area and Severity Index scoring system. Histologic scores were graded with a 5-point grading scale. Complete blood cell count was obtained at the beginning and at the end of the study. Thyroid-stimulating hormone (TSH) was obtained at the beginning and every 2 weeks thereafter until completion of the study. RESULTS: Three patients dropped out of the study. Of the remaining seven, two showed near-complete resolution of their psoriatic lesions, whereas the remainder showed moderate improvement in their clinical scores. Histologic scores were significantly improved in the group with all but one patient showing improvement or no change. Thyroid function tests were unchanged in all but one patient who showed a slight increase in serum TSH at the sixth week of therapy. CONCLUSION: Because of its low toxicity relative to other oral treatments of psoriasis, PTU may have a role in the treatment of patients with this disorder.

Administration, Oral↗
PubMed1993

Serum ICAM-1 concentrations in patients with psoriasis treated with antithyroid thioureylenes.

Serum concentrations of intercellular adhesion molecule-1 (ICAM-1), a marker of early T-cell activation were measured in 14 patients with stable plaque psoriasis who received treatment for 8 weeks with the antithyroid thioureylenes, propylthiouracil (PTU) or methimazole (MMI) which have been previously shown to produce significant improvement in such patients. Baseline serum concentrations of ICAM-1 were significantly higher in the patients with psoriasis compared with normal control volunteers. Following therapy with either PTU (300 mg daily) or MMI (40 mg daily) serum ICAM-1 concentrations did not decline significantly. Since ICAM-1 expression on vascular endothelium increases in active psoriasis, and is postulated to promote T-cell migration to and retention at these sites, it is hypothesized that the beneficial therapeutic effects of thioureylenes in psoriasis occur distal to the events that lead to lymphocyte migration to vascular structures in the dermis.

Adult↗
PubMed1993

Effect of propylthiouracil and methimazole on serum levels of interleukin-2 receptors in patients with psoriasis.

BACKGROUND: We have previously reported clinical improvement in patients with psoriasis who received orally administered antithyroid thioureylenes, propylthiouracil (PTU), and methimazole (MMI). The antithyroid drugs are believed to exert immunomodulatory effects based on the results of studies in patients with Graves' disease, the only disease in which they are clinically used. The potential of these drugs to mediate clinical improvement in patients with psoriasis by reducing expression of the interleukin-2 receptor (IL2R), a marker of early T and B cell activation, was addressed in the present study. METHODS: Baseline serum concentrations of IL2R were measured by an enzyme-linked immunosorbant assay (ELISA) in 15 patients with stable plaque psoriasis and in the same patients after 8 weeks of oral therapy with either 300 mg of propylthiouracil (n = 7) or 40 mg methimazole (n = 8) given daily. Baseline values were compared with normal controls. RESULTS: Serum IL2R concentrations in the psoriatic patients were significantly higher than in normal controls. After treatment with PTU or MMI, IL2R serum concentrations were not significantly reduced either in the group as a whole or separately in the PTU and MMI treated patients. CONCLUSIONS: Since elevated serum concentrations of IL2R often reflect T and B cell activation, and elevated IL2R serum levels are seen in several autoimmune diseases, it is speculated that the beneficial effect of thioureylenes in patients with psoriasis is mediated by some mechanism(s) other than reduction of IL2R expression in activated lymphocytes.

Adult↗
PubMed1993

Methimazole (2-mercapto 1-methyl imidazole) in psoriasis--results of an open trial.

Methimazole, an antithyroid drug, was orally administered, in an open trial, in a dose of 20 mg every 12 h for 8 weeks to 8 volunteers with long-standing psoriasis. 3-mm punch biopsies were taken from the lesions at the start and at the end of the study. Clinical response was assessed using the Psoriasis Areas Severity Index score. Methimazole produced marked to moderate improvement in the clinical scores in the majority of patients. Histological scores were also significantly improved in all patients. Unexpectedly, thyroid function tests were not affected by methimazole therapy in all but one patient, and none of the patients developed drug-induced cytopenia. Methimazole may be an effective therapeutic agent in the management of psoriasis; it most probably exerts its therapeutic effect by acting on the immune system.

Adult↗
PubMed1992

Synthesis and evaluation of radioiodinated 2-(2(RS)-aminopropyl)-5- iodothiophenes as brain imaging agents.

Methods have been developed for the preparation of 2-(2(RS)-aminopropyl)-5-iodothiophenes. The syntheses and physical properties of 2-(2(RS)-aminopropyl)-5-iodothiophene and N-isopropyl-2-(2(RS)-aminopropyl)-5-iodothiophene are described. The radioiodinated agents are of interest because of the high expected uptake and prolonged brain retention that may result from binding to high-capacity, relatively nonspecific amine binding sites. Radioiodine was introduced into the 5-position of 2-(2(RS)-aminopropyl)-5-iodothiophene and N-isopropyl-2-(2(RS)-aminopropyl)-5-iodothiophene by radioiodination of the corresponding 5-boronic acid or 5-(trimethylstannyl) derivatives. Tissue distribution studies in rats with 2-(2(RS)-aminopropyl)-5-[125I]iodothiophene showed high brain uptake (5 min, 2.77% dose/g; 30 min, 2.51% dose/g) and good brain/blood (B/B) ratios (5 min, 6/1; 30 min 3.8/1. A comparison of the brain uptake of the N-isopropyl derivative with the 2(RS)-aminopropyl analogue demonstrated higher initial brain uptake and brain to blood ratios (5 min, 3.2% dose/g; 10.3/1) but more rapid washout (30 min, 1.37% dose; 2.8/1). These data suggest that radiolabeled 2-(2(RS)-aminopropyl)-5-iodothiophenes are potentially useful agents for cerebral perfusion imaging by single-photon-emission computerized tomography (SPECT).

Animals↗
PubMed1992

Treatment of lupus pernio with the flashlamp pulsed dye laser.

Lupus pernio, a form of cutaneous sarcoidosis usually affecting the face, is often disfiguring and resistant to therapies, both medical and surgical. To our knowledge, there have been no previous reports of laser therapy for this condition. We describe a case of nasal lupus pernio successfully managed with the flashlamp pulsed dye laser.

Adult↗
PubMed1992

Cyclosporine therapy for psoriasis: a cell cycle-derived dosing schedule.

BACKGROUND: Cyclosporine is effective in the treatment of psoriasis; however, potentially serious side effects limit its long-term use. On the basis of the 36-hour psoriatic keratinocyte cell cycle, a new dosing regimen was investigated. OBJECTIVE: The purpose of this study was to evaluate a 36-hour weekly dosing schedule with cyclosporine for the treatment of psoriasis, in an attempt to decrease side effects while maintaining efficacy. METHODS: Fifteen patients were studied by means of oral doses of cyclosporine taken at 12-hour intervals for three doses per week during a 10-week period. The initial dose, 2.5 mg/kg/dose (7.5 mg/kg/wk), was increased every 2 weeks by 2.5 mg/kg/dose to a maximum of 10 mg/kg/dose. RESULTS: The average improvement as assessed by the Psoriasis Area and Severity Index for all 15 patients was 61%. Six patients had a more than 75% improvement, three patients improved 50% to 74%, and six patients improved less than 50%. Three patients dropped out because of adverse side effects, and three others completed the study at a reduced dose. CONCLUSION: It is concluded that, although effective, this dosing regimen may not have an advantage over daily dosing, given its side effect profile and the need to go to relatively high doses every 24 hours.

Adult↗