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B Goldberg

Publications and source records attributed to B Goldberg.

At least 19 recordsLinked to original sources

Inhibition of Trichomonas vaginalis ornithine decarboxylase by amino acid analogs.

Ornithine decarboxylase (ODC) from Trichomonas vaginalis was inhibited irreversibly by several substrate analogs. Of these, DL-alpha-monofluoromethyldehydroornithine (MFMDO) and DL-alpha-monofluoromethylornithine (MFMO) were the most potent. The enzyme was unaffected by putrescine analogs suggesting that differences exist between the regulation of the trichomonad enzyme and that in other eukaryotes. In culture the ornithine analogs strongly inhibited putrescine synthesis and increased the generation time after 24 hr of exposure. In a semi-defined growth medium MFMDO methyl and ethyl esters increased the generation time from 4.5 hr to 9.0 and 8.2 hr, respectively. In standard undefined growth medium the trichomonad ODC was fully induced only after 15 hr (late log) and had an extended half-life of greater than 8 hr.

Amino Acids

Origin of AIDS.

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Acquired Immunodeficiency Syndrome

Cure of murine Trypanosoma brucei rhodesiense infections with an S-adenosylmethionine decarboxylase inhibitor.

The compound 5'-([(Z)-4-amino-2-butenyl]methylamino)-5'-deoxyadenosine (MDL73811), a potent inhibitor of S-adenosylmethionine decarboxylase, was effective in mice against six of eight clinical isolates of Trypanosoma brucei rhodesiense, the causative agent of East African sleeping sickness. In combination with the ornithine decarboxylase inhibitor DL-alpha-difluoromethylornithine (DFMO; Ornidyl), MDL73811 acted synergistically to cure seven of eight infections. MDL73811 was effective when given singly at 50 to 100 mg/kg of body weight per day for 7 days (osmotic pumps). In combination with subcurative DFMO levels (0.25 to 1.0% in drinking water for 7 days), the curative MDL73811 dose could be lowered to 25 or 50 mg/kg, depending on the isolate. Oral administration of the MDL73811-DFMO combination was also effective in an acute infection and in a long-term central nervous system model of Trypansoma brucei brucei infection. These data indicate that MDL73811 may be effective therapeutically in drug-refractory and late-stage East African trypanosomiasis.

Adenosylmethionine Decarboxylase

Differential sensitivity of Trypanosoma brucei rhodesiense isolates to in vitro lysis by arsenicals.

Clinical isolates of Trypanosoma brucei rhodesiense, which were resistant to arsenical drugs in murine infections, were examined for resistance in vitro. A rapid lysis assay was developed which was able to predict in vivo sensitivity to melarsoprol (Mel B, Arsobal) and melarsen oxide. The assay was based on the finding that long slender bloodforms of drug-sensitive isolates would lyse in the presence of arsenicals upon incubation in heat-inactivated fetal bovine serum. On the basis of plots of decrease in the absorbance of trypanosome suspensions vs time of incubation with drug, L50 values, reflecting the drug concentration necessary for lysis of 50% of the cells within 30 min. were calculated for five strains. These values ranged from less than 30 microM for arsenical-sensitive strains to greater than 75 microM in proven arsenic refractory isolates. Calcium was essential for lysis, and the presence of the Ca2+ chelator EGTA (10 mM) in serum delayed lysis of sensitive strains. Ca2+ channel antagonists (Verapamil, Diltiazem), however, did not enhance lysis of refractory isolates when used at 20 to 30 microM. Intracellular concentrations of reduced trypanothione, the apparent target of arsenicals, were similar for all isolates, approximately 1.02 +/- 0.28 nmol/10(8) cells, as detected by monobromobimane derivitization and HPLC analysis. Uptake of melarsen oxide was found to be reduced in arsenical refractory strains. Uptake was judged by reduction of free reduced trypanothione as a result of formation of the trypanothione-arsenic complex Mel T. Little change was found in arsenical-resistant strains, but sensitive strains had 50 to 70% reductions in trypanothione levels after incubation with a low (1 microM) level of melarsen oxide.

Animals

A double-blind, multicenter comparison of 0.05% halobetasol propionate ointment and 0.05% clobetasol propionate ointment in patients with chronic, localized plaque psoriasis.

In a double-blind, parallel-group, multicenter trial in 134 patients with severe, localized, plaque psoriasis, the success rate (described as "healed" or "marked improvement") at the end of the study was 96% in the halobetasol propionate group and 91% in the clobetasol propionate group. A significantly larger proportion of patients treated with halobetasol had no disease or mild disease after 14 days compared with those treated with clobetasol (86% versus 70%, p = 0.023). Healing within 24 days of starting treatment was noted in 69% and 56% of patients treated with halobetasol and clobetasol, respectively. Adverse effects were reported in a smaller percentage of patients treated with halobetasol propionate ointment than in those treated with clobetasol propionate ointment (7% versus 12%). Cosmetic acceptability and ease of application were recorded as "very good" in a larger percentage of patients treated with halobetasol propionate ointment than in the group treated with clobetasol propionate (90% versus 80%).

Adult

The orthopaedist as prosthetic team leader: getting the best for your patient from the team.

In summary, care of the amputee is an ongoing process, from evaluation and treatment of the initial disease or traumatic event, through fabrication and fitting of the prosthesis, to the amputee's return to as normal a lifestyle as possible. It is a process that has evolved over the years into a distinct approach designed to get the best for the patient from the team.

Amputation, Surgical

Superoxide generation and its modulation by adenosine in the neutrophils of subjects with asthma.

Airway inflammation with neutrophil infiltration may play a role in airway hyperreactivity. Neutrophils may exert their effects through the generation of superoxide O2- anion and other oxygen-derived free radicals. O2- generation by neutrophils has been demonstrated to be modulated by adenosine at physiologic concentrations. Therefore, we have investigated the function of peripheral blood neutrophils with respect to O2- anion generation and its regulation by adenosine in both subjects with asthma and normal subjects and also the relationship between O2- anion generation and airway hyperresponsiveness in subjects with asthma. Purified neutrophils were obtained from eight subjects with stable asthma and seven normal control subjects not taking chronic medications. O2- anion generation in subjects with asthma was significantly higher compared with that of normal subjects after stimulation with either N-formyl-methionyl-leucyl-phenylalanine (mean, 14.8 nmol/10(6) cells for subjects with asthma versus mean, 9.6 nmol/10(6) cells for normal subjects; p less than 0.01) or phorbol myristate acetate (mean, 13.6 nmol/10(6) cells versus mean, 8.1 nmol/10(6) cells; p less than 0.05). Adenosine inhibited N-formyl-methionyl-leucyl-phenylalanine-stimulated O2- anion generation in a dose-related fashion in subjects with asthma and normal subjects to a similar degree. Adenosine had no effect on O2- anion generation after phorbol myristate acetate stimulation. These results indicate that neutrophils from subjects with asthma produce more O2- anion when they are stimulated than do neutrophils from normal subjects and that this difference is not due to adenosine modulation. In subjects with asthma, O2- anion generation correlated with the degree of airway hyperresponsiveness to inhaled methacholine.

Adenosine

The lead program at CPRI.

A lead (Pb) screening program in operation at CPRI in London, Ontario, since 1977 involves simultaneous measurement of blood Pb and erythrocyte protoporphyrin (EP) in a randomized population of physically and/or mentally handicapped children and adolescents on admission, discharge and during outpatient visits. This 11-year study has yielded a large database for computerized evaluation. Based upon log normal transformation of data obtained from the admission and outpatient groups, the normal curve yielded a mean and standard deviation (SD) for blood Pb of 0.36 +/- 0.27 mumol/L (n = 4188). This fosters a downward revision of the upper reference limit to 0.89 mumol/L (95% confidence level). The overall mean for EP was 0.35 +/- 0.37 mumol/L and suggests an upper reference limit of 1.09 mumol/L. The direct correlation between annual means of blood Pb and EP retained its significance (r = 0.80; P less than 0.004). For both blood Pb and EP, there was no significant difference in values between admissions (n = 1455), discharges (n = 1310) and outpatient visits (n = 2963). Only in the case of blood Pb was the overall mean value of males (n = 3822) higher (0.46 +/- 0.34 mumol/L) than that of females (0.39 +/- 0.25 mumol/L; n = 1906), but by t-test the difference was not significant. Although annual means of both blood Pb and EP were highest in 1978 and 79 and lowest in 1987, there was no significant difference between any two years.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent

Mentally retarded adolescent sex offenders. A survey and pilot study.

There is not a great deal of empirical research on adolescent sex offenders and even less on mentally retarded adolescent sex offenders. This study provides some preliminary data in this area. Results of a survey of the extent and types of sexual problems evident amongst groups of mentally retarded and intellectually normal adolescents (N = 196), seen at an assessment and treatment centre in southwestern Ontario during a 14 month period is presented. In addition three groups of ten adolescents each (mentally retarded and intellectually normal sex offenders and one group of mentally retarded non-offenders with behavioural problems) were investigated to gain a more indepth perspective of characteristics of these adolescents and their backgrounds. Considering the high recidivism rate for these groups, indications for treatment are discussed with special consideration for the mentally retarded offenders.

Adolescent

CCK inhibits real and sham feeding in gastric vagotomized rats.

We tested both sham feeding and real feeding in gastric vagotomized rats equipped with chronic gastric cannulas, either without pretest food deprivation or after 18 hr food deprivation. In each condition, 0.3-4 micrograms/kg CCK inhibited food intake similarly in control and vagotomized rats. Behavioral observations indicated the presence of normal postprandial satiety after CCK. We then tested real feeding in noncannulated rats after either total abdominal vagotomy, gastric vagotomy, or control operation. Doses of 0.5-4 micrograms/kg CCK had no effect on food intake after total vagotomy, but again inhibited feeding with equal potency in gastric vagotomized and control rats. The inhibitory effect of 6 micrograms/kg CCK was attenuated but not blocked by total vagotomy. Finally, we tested rats with gastric cannulas after gastric plus celiac vagotomy. CCK also inhibited both real and sham feeding after this lesion. These data confirm previous findings that abdominal vagal fibers mediate the satiety effect of moderate intraperitoneal doses of CCK, but fail to support the hypothesis that gastric branch fibers are the necessary vagal contribution.

Animals

Proliferation of eccrine sweat ducts associated with alopecia areata.

Proliferation of sweat ducts has been described as a reactive process in a variety of benign and malignant neoplasms and inflammatory conditions in the skin, including scarring alopecia. However, to our knowledge this phenomenon has not been observed in non-scarring alopecia. The following case documents such a proliferation arising in an alopecia consistent with alopecia areata. An 83-year-old female developed progressive, fairly well circumscribed patches of alopecia over a 2-3 year period. Unequivocal scarring was not present. Histopathological examination revealed non-scarring alopecia with miniaturized and telogen follicles and a proliferation of eccrine ductal structures in the reticular dermis. These ductal structures varied in size and degree of cystic dilatation and resembled a primary eccrine neoplasm, such as syringoma. Only minimal focal fibrosis was observed in association with the eccrine proliferation. In summary, this case indicates that eccrine sweat duct proliferation may occur in non-scarring alopecia and must be differentiated from a primary eccrine neoplasm.

Aged