Biomedical subjects

R M Berman

Publications and source records attributed to R M Berman.

27 records · Page 2Linked to original sources

PubMed1996

Tumor-targeting potential of radioiodinated iododeoxyuridine in bladder cancer.

UNLABELLED: Since bladder cancer arises in the superficial lining of the urothelium, it is a likely candidate for site-directed administration of 5-iodo-2'-deoxyuridine radiolabeled with the Auger electron emitter 123I or 125I (*IUdR). METHODS: We instilled *IUdR for 2 hr directly within the bladder lumen of rats bearing N-methyl-N-nitrosourea (NMU)-induced bladder cancer and conducted scintigraphic, biodistribution and autoradiography (ARG) studies 48 hr and 1 wk later. Control animals were not subjected to the carcinogen but were instilled with *IUdR. RESULTS: Two groups of animals were identified after instillation of MNU: Group A consisted of rats with hyperplasia and Group B of rats with papillary carcinoma (stages Ta and T1). Scintigraphic detection of carcinomas was achieved with high sensitivity and specificity, and increased tumor-to-normal tissue ratios were obtained in both groups. Moreover, ARG demonstrated that (1) the uptake of *IUdR was observed in the hyperplastic and carcinomatous urothelium but not in the normal urothelium; (2) uptake was detected at a very early stage of tumor development (hyperplasia stage); (3) *IUdR was able to penetrate deep within the bladder wall; and (4) other normal dividing tissues, such as the bone marrow, the small intestine and the large intestine, were free of silver grains (i.e., no DNA-incorporated *IUdR). CONCLUSION: Since this carrier of Auger electron emitters has antineoplastic effects ([123I]IUdR and [125I]IUdR) in addition to its scintigraphic potential ([123I]IUdR and [131I]IUdR), it holds promise for therapy and early diagnosis of bladder cancer.

Animals↗

PubMed1993

A method for detection of hydroxyl radicals in the vicinity of biomolecules using radiation-induced fluorescence of coumarin.

A novel method is described to quantitate radiation-induced hydroxyl radicals in the vicinity of biomolecules in aqueous solutions. Coumarin-3-carboxylic acid (CCA) is a non-fluorescent molecule that, upon interaction with radiation in aqueous solution, produces fluorescent products. CCA was derivatized to its succinimidyl ester (SECCA) and coupled to free primary amines of albumin, avidin, histone-H1, polylysine, and an oligonucleotide. When SECCA-biomolecule conjugates were irradiated, the relationship between induced fluorescence and dose was linear in the dose range examined (0.01-10 Gy). The fluorescence excitation spectrum of irradiated SECCA-biomolecule conjugates was very similar to that of 7-hydroxy-SECCA-biomolecule conjugates, indicating the conversion of SECCA to 7-hydroxy-SECCA following irradiation. Control studies in environments that excluded certain radiation-induced water radicals for both the conjugated and unconjugated forms of irradiated SECCA demonstrated that: (1) the induction of fluorescence is mediated by the hydroxyl radical; (2) the presence of oxygen enhances induced fluorescence by a factor of about 1.4, and (3) other primary water radicals and secondary radicals caused by interaction of primary water radicals with biomolecules do not significantly influence the induced fluorescence. The data indicate that the induction of fluorescence on SECCA-biomolecule conjugates records specifically the presence of the hydroxyl radical in the immediate vicinity of the irradiated biomolecule. The method is rapid and sensitive, uses standard instrumentation, and the sample remains available for further studies.

Avidin↗

PubMed1993

Morphological, biochemical, and molecular changes in endothelial cells after alpha-particle irradiation.

The response of cultured bovine aortic endothelial (BAE) cells after exposure to alpha-particle radiation from chelated 212Bi has been evaluated. The results suggest that even relatively high doses of alpha-particle radiation from 212Bi (20-72 Gy) cause only minor acute changes in the morphology of BAE cells (light and electron microscopy) under conditions of confluent monolayer growth. Significant morphological changes can be detected in cells that detach from the monolayer, though it is unclear whether these changes represent a genuine response to irradiation or reflect the causes or effects of monolayer detachment with the consequent loss of intercellular biochemical communication. After alpha-particle irradiation (20-40 Gy) angiotensin-converting-enzyme activity was not detectable in the monolayer culture medium but was significantly decreased within the cell monolayer. Neutral-elution-assay data demonstrated that DNA double-strand-break (DSB) damage occurred in these cells and that about 35% of the DSBs were repairable.

Alpha Particles↗

PubMed1992

DNA damage produced in V79 cells by DNA-incorporated iodine-123: a comparison with iodine-125.

The neutral elution technique (pH 9.6) has been used to compare the damage produced in the DNA of V79 cells following the decay of the Auger-electron emitters 123I and 125I incorporated into DNA in the form of 5-[123I/125I]iodo-2'-deoxyuridine (123IdU, 125IdU) or after 60Co gamma irradiation. Elution profiles of retained radioactivity versus eluted volume were generally found to be nonlinear and partially dependent on the cell treatment prior to elution. Plots of a suitable function of radioactivity retention on the filters versus total decays for 123I or 125I and dose (Gy) for gamma radiation were linear. Assuming that each 125I decay produces one double-strand break (DSB), the 60Co efficiency in DSB production was found to be 53.4 DSBs/Gy/cell (or 17.8 DSBs/Gy/10(12) Da), in agreement with values reported previously. The decay of 123I led to 0.74 DSB/decay/cell if decays occurring only during nonrepair conditions were counted. This DSB production efficiency is in agreement with Monte Carlo semiempirical models of the action of radiation on DNA.

Animals↗

PubMed1991

5-[123I]iodo-2'-deoxyuridine in the radiotherapy of an early ascites tumor model.

The extreme biological toxicity of Auger emitters is caused by the decay-associated, highly localized deposition of energy. The antineoplastic capability of an Auger-electron emitter, iodine-123, incorporated into the thymidine analog, 5-iodo-2'-deoxyuridine (IUdR) was evaluated in an intraperitoneal (i.p.) murine ovarian tumor (MOT) in female C3HeB/FeJ mice. Total doses of 0.37 to 8.88 MBq (10-240 microCi) 123IUdR were administered i.p. in five equally divided fractions at 24, 28, 32, 36, and 40 hr after the i.p. inoculation of 0.5 to 1.6 x 10(6) tumor cells per mouse. Control tumor-bearing animals were injected with identical volumes of saline at 4-hr intervals. Biodistribution studies demonstrated a distinct and localized uptake of 123IUdR in the MOT cells (1% of the injected dose was associated with MOT cells 24 hr after the last injection), whereas in animals without tumor there was no radioactivity associated with the peritoneal cells. Analogous results were obtained from scintigraphic images where the focal area of abdominal activity persisted only in MOT-bearing mice while it cleared from the abdomen of the controls. The 50% survival (median survival) of the control group was 19 days for an inoculum of 1.6 x 10(6) MOT cells per animal, whereas the median survival of MOT-bearing animals treated with 123IUdR increased by 11 days for the highest administered dose (8.88 MBq, 240 microCi) and resulted in a 20% absolute survival at 7 weeks. Statistically significant absolute survival prolongation was found with all of the total administered doses. The prolongation of both median and absolute survival time of the tumor-bearing animals treated with 123IUdR conclusively indicates the substantial antineoplastic activity of the Auger-electron emitter iodine-123.

Animals↗

PubMed1986

Octapeptides deduced from the neuropeptide receptor-like pattern of antigen T4 in brain potently inhibit human immunodeficiency virus receptor binding and T-cell infectivity.

The differentiation antigen T4, present on the helper/inducer subset of T lymphocytes, is thought to serve as the receptor for the human immunodeficiency virus (HIV). We find that a 60-kDa protein, immunoprecipitable by monoclonal antibody (mAb) OKT4, is present on membranes from human brain as well as human T cells. Furthermore, the radioiodinated HIV envelope glycoprotein [125I-labeled gp120 (125I-gp120)] can be specifically covalently affixed to a molecule present on rat, monkey, and human brain membranes to yield a complex that is indistinguishable from that formed on human T cells. T4 antigen has been studied on unfixed squirrel monkey, rat, and human brain sections by autoradiography using the mAb OKT4. A highly conserved neuroanatomical pattern has been demonstrated, suggesting an analogous organization in these three mammalian brains. Furthermore, the localization of 125I-gp120 receptor binding appears similar to that of T4 and is highly reminiscent of patterns for many previously characterized neuropeptide receptors. A computer-assisted analysis of gp120 suggested that a previously unremarkable octapeptide sequence within the gp120 protein, which we have synthesized and termed "peptide T," may play an important role in HIV attachment. Thus, peptide T and three rationally designed peptide analogs, each with a systematic amino acid substitution, potently inhibit specific 125I-gp120 binding to brain membranes. Additionally, when tested in a viral infectivity assay, these peptides show the same rank order and similar absolute potency to block HIV infection of human T cells. Thus, peptide T may provide a useful pharmacological or immunological basis for the control and treatment of AIDS.

Amino Acid Sequence↗

PubMedDate not supplied

Bulimia nervosa and alcohol dependence. A case report of a patient enrolled in a randomized controlled clinical trial.

Bulimia nervosa and alcohol use disorders frequently co-occur. A review of the literature, however, reveals a paucity of information on treatment of patients with these comorbid conditions. We present a case report of a 34-year-old Caucasian female with a 20-year history of bulimia nervosa with co-occurring alcohol dependence, who participated in a randomized placebo-controlled medication augmentation trial for bulimia nervosa. The patient served as a pilot subject who met the exclusionary criterion of alcohol dependence, but received all the assessment and intervention procedures of the clinical trial for bulimia nervosa. Despite double-blind random assignment to a placebo condition, the patient's symptoms of bulimia nervosa substantially improved over the course of the 5-week efficacy trial. We hypothesize that this improvement was due to concurrent abstinence from alcohol rather than a placebo effect.

Adult↗

PubMedDate not supplied

NMDA agonists and antagonists as probes of glutamatergic dysfunction and pharmacotherapies in neuropsychiatric disorders.

Antagonists of the N-methyl-D-aspartate (NMDA) subclass of glutamate receptors and agonists of the glycine-B coagonist site of these receptors have been important tools for characterizing the contributions of NMDA receptor pathophysiology to a large number of neuropsychiatric conditions and for treating these conditions. Among these disorders are Alzheimer's disease, chronic pain syndromes, epilepsy, schizophrenia, Parkinson's disease, Huntington's disease, addiction disorders, major depression, and anxiety disorders. This review will examine pathophysiological and therapeutic hypotheses generated or supported by clinical studies employing NMDA antagonists and glycine-B agonists and partial agonists. It will also consider ethical issues related to human psychopharmacological studies employing glutamatergic probes.

Brain Diseases↗

PubMedDate not supplied

Immunoradiometric assay for antibodies recognizing antigenic gangliosides.

An immunoradiometric assay for monoclonal antibodies (MoAb) recognizing gangliosides as antigens (Ag) is described and exemplified by the determination of the immunoreactive fraction of 125I-radiolabeled monoclonal A2B5 and 3G5 IgM antibodies. The assay was performed in 96-well microtiter plates equipped with cellulose filter membranes, using the antigens extracted from cloned rat insulinoma cells (RINm5F). The selectivity of the assay was demonstrated by studying the interactions of A2B5 and 3G5 with specific Ag and irrelevant gangliosides. The binding of 125I-A2B5 and 125I-3G5 to the RINm5F extract containing Ag exceeded 35% of the total applied radioactivity and depended on the degree of protein damage caused by radiolabeling, whereas irrelevant glycolipids bound 0.4% (s.d. 0.3%) of total applied 125I-3G5 and 1.2% (s.d. 0.3%) of 125I-A2B5 regardless of the initial amount of the radiolabeled MoAb used. Additional support for the specificity of this method was acquired in experiments with the A1D2 IgG antibody that interacts with a glycoprotein expressed by RINm5F cells but not with the gangliosidic antigens present in the same cell line. 125I-A1D2 bound neither Ag (0.47%; s.d. 0.12%) nor brain extracts containing irrelevant gangliosides (0.32%; s.d. 0.17%). The data for the specific MoAb-Ag systems were analyzed using a modified Lineweaver-Burk graph. By plotting the reciprocal of the fraction of specifically bound MoAb versus the reciprocal of the antigen concentration, the immunoreactive fraction was determined. The present method is rapid, convenient, and independent of variability in antigen expression on the cell surface.

Antibodies, Monoclonal↗