Search PubMed⌕ Search

Biomedical subjects

N Goldstein

Publications and source records attributed to N Goldstein.

At least 37 records · Page 2Linked to original sources
PubMed1997

Neutralizing antibodies against epidermal growth factor and ErbB-2/neu receptor tyrosine kinases down-regulate vascular endothelial growth factor production by tumor cells in vitro and in vivo: angiogenic implications for signal transduction therapy of solid tumors.

The overexpression in tumor cells of (proto)-oncogenic receptor tyrosine kinases such as epidermal growth factor receptor (EGFR) or ErbB2/neu (also known as HER-2) is generally thought to contribute to the development of solid tumors primarily through their effects on promoting uncontrolled cell proliferation. However, agents that antagonize the function of the protein products encoded by these (proto)-oncogenes are known to behave in vivo in a cytotoxic-like manner. This implies that such oncogenes may regulate critical cell survival functions, including angiogenesis. The latter could occur as a consequence of regulation of relevant growth factors by such oncogenes. We therefore sought to determine whether EGFR or ErbB2/neu may contribute to tumor angiogenesis by examining their effects on the expression of vascular endothelial cell growth factor (VEGF)/vascular permeability factor (VPF), one of the most important of all known inducers of tumor angiogenesis. We found that in vitro treatment of EGFR-positive A431 human epidermoid carcinoma cells, which are known to be heavily dependent on VEGF/VPF in vivo as an angiogenesis growth factor, with the C225 anti-EGFR neutralizing antibody caused a dose-dependent inhibition of VEGF protein expression. Prominent suppression of VEGF/VPF expression in vivo, as well as a significant reduction in tumor blood vessel counts, were also observed in established A431 tumors shortly after injection of the antibody as few as four times into nude mice. Transformation of NIH 3T3 fibroblasts with mutant ErbB2/neu, another EGFR-like oncogenic tyrosine kinase, resulted in a significant induction of VEGF/VPF, and the magnitude of this effect was further elevated by hypoxia. Moreover, treatment of ErbB2/neu-positive SKBR-3 human breast cancer cells in vitro with a specific neutralizing anti-ErbB2/neu monoclonal antibody (4D5) resulted in a dose-dependent reduction of VEGF/VPF protein expression. Taken together, the results suggest that oncogenic properties of EGFR and ErbB2/neu may, at least in part, be mediated by stimulation of tumor angiogenesis by up-regulating potent angiogenesis growth factors such as VEGF/VPF. These genetic changes may cooperate with epigenetic/environmental effects such as hypoxia to maximally stimulate VEGF/VPF expression. Therapeutic disruption of EGFR or ErbB2/neu protein function in vivo may therefore result in partial suppression of angiogenesis, a feature that could enhance the therapeutic index of such agents in vivo and endow them with anti-tumor effects, the magnitude of which may be out of proportion with their observed cytostatic effects in monolayer tissue culture.

Adenocarcinoma↗
PubMed1997

[Superoxide inhalation as adjuvant therapy in children with bronchial asthma].

The aim of the present investigation was to confirm results of an earlier pilot study on the adjuvant treatment of atopic asthmatics using superoxide inhalation in a double blind placebo controlled experiment. Group 1 (verum) included 28 patients (7 girls and 21 boys whose age was 12.2c2.9 years) and Group 2 (placebo) comprised 23 (8 girls and 15 boys aged 11.7c3.2 years). Fifteen-minute superoxide inhalations were used as adjuvant therapy to the routine treatment. The patients underwent spirometry, blood analysis, nasal smear tests for eosinophils, and questionnaires. The worse the baseline parameters were, the better their spirometric ones were. This was reflected by higher significant correlations between the baseline values and their changes in peak flowmetry, FEV1, and FEF and by the patients' grouping by the baseline limitation of respiratory functions (less than 80% or more of the individual normal values). The most significant improvement (46.5%; p = 0.008) was observed in the subgroup with VC. In accordance with subjective assessment data, the time course of reductions in the frequency and severity of asthma attacks and coughing fits, and sputum amount was significantly better in Group 1 than in Group 2. The findings are interpreted as a result of an alleviated inflammatory process due to superoxide inhalation-induced oxidative training in patients.

Administration, Inhalation↗
PubMed1996

Exogenous gaseous superoxide potentiates the antinociceptive effect of opioid analgesic agents.

The study examined the potentiation of the antinociceptive action of opioid analgesics produced by gaseous superoxide (GS) in the rat hind paw withdrawal test (PWT) and by GS or hydrogen peroxide (HP) in the formalin test. In the PWT, inhalation of GS for 50 minutes before i.p. injection of threshold doses of morphine (0.5 mg/kg) and trimeperidine (1.0 mg/kg) increased the threshold of nociception (TN) by a maximum of 43.0% (p < 0.05) and 113.4% (p < 0.01) respectively. The GS/trimeperidine-dependent increase in TN showed two peaks, the second of which could be suppressed by nialamide. Naloxone abolished the GS/ morphine-dependent increased in the TN. In the formalin test, a significant antinociceptive effect developed after GS inhalation or HP administration (intranasally, 2 x 5 microliters of 2 x 10(-5) mol/l solution in saline) in combination with low doses of Omnopon (0.06-0.75 mg/kg). These results suggest that both GS and HP potentiate the antinociceptive effects of opioid analgesics.

Analgesics, Opioid↗
PubMed1994

High-level expression of a biologically active human interleukin-6 mutein.

We have constructed two different muteins of interleukin-6 (IL-6) which were expressed in Escherichia coli. Both muteins lack the first 22 N-terminal amino acids of native IL-6 and lack one or the other of the two naturally occurring pairs of cysteines at either position 45 and 51 or position 74 and 84 of IL-6. We found that there was a dramatic increase in the level of IL-6 produced from each mutein clone, compared to the level produced by the wild-type IL-6 clone. We also observed that the yield of soluble and properly refolded mutein IL-6 was highest when the cysteines at position 74 and 84 were left intact. The mutein IL-6 with cysteines at position 74 and 84 was as active as wild-type IL-6 and a lower concentration of the mutein IL-6 was required to reach maximal activity, compared to wild-type IL-6. The mutein IL-6 with cysteines at position 45 and 51 had a much reduced biological activity.

Animals↗
PubMed1994

An outbreak of foodborne streptococcal throat infection.

Streptococcal pharyngitis is a common disease of epidemic nature, usually transmitted by saliva droplets. We present an epidemiologic analysis of an outbreak of streptococcal pharyngitis in a military unit involving 75 soldiers. The causing organism was Streptococcus pyogenes (group A beta hemolytic Streptococcus, T28 M56), which was isolated from 53 affected individuals. The source of the epidemic was probably an army cook. The infection was transferred by a cabbage salad to individuals who became symptomatic within 24-48 h. This epidemic is a reminder of an exceptional route of streptococcal dissemination and one of the largest outbreaks of foodborne streptococcal pharyngitis documented.

Disease Outbreaks↗
PubMed1993

The use of a novel immune complex to isolate neutralizing antibodies to basic fibroblast growth factor.

This paper describes the use of a novel immune complex (IC) to generate neutralizing monoclonal antibodies to basic fibroblast growth factor. The IC uses a non-neutralizing monoclonal antibody bound to Protein A, itself coated on a solid support, to capture the antigen. Presumably, the capture antibody binds to a region of the antigen distal from the neutralizing site. Animals, immunized with the IC, develop a neutralizing titer and hybridomas producing neutralizing antibodies to basic FGF were obtained. This method can be used to generate neutralizing monoclonals to highly conserved growth factors whenever the antigen can be captured at a site distal to the neutralizing eptiopes.

3T3 Cells↗
PubMed1993

Skin cancers in Hawaii (1993).

Basal cell cancers are the most common of all cancers. They rarely metastasize and very rarely kill. Melanomas, however, do kill! An estimated 20 people in Hawaii will die this year from malignant melanoma. Early diagnosis and treatment can save much morbidity--surgery, scars and other defects--and can save lives. This manuscript reviews melanoma data from several agencies in Hawaii and from the experience of the author's private practice. In his private practice, he has seen the incidence of melanomas jump from an average of one a year in 1970 to 1975 to 7.4 each year between 1986 and 1990. While basal cell cancers and melanomas occur more in Caucasians, they are seen in all races. Everyone can get skin cancer and melanoma. Physicians must teach their patients to Practice Safe Sun--Hawaii.

Adult↗
PubMed1992

Epidemiology of bladder emptying symptoms in elderly men.

We provide estimates of the prevalence, incidence and remission of difficult bladder emptying symptoms (prostatism) among noninstitutionalized men 60 years old and older living in a community in the United States. The prevalence of 1 or more symptoms of prostatism (hesitancy, straining, weak stream, intermittency or use of a catheter) among men who never had prostatic surgery is 35%. The annual incidence rates during years 1 and 2 of followup were 16.4% and 16.1%, respectively. Remission of symptoms of prostatism also was observed. Of the respondents with severe symptoms at baseline 22.9% were asymptomatic 1 year later. The prevalence of prostatic surgery in this population was 20%. The annual incidence rates during years 1 and 2 of followup were 2.6% and 3.3%, respectively. Urological and nonurological correlates of prostatism are identified. The irritative bladder symptoms are all significantly associated with moderate to severe bladder emptying symptoms (p < 0.0005). Nonurological conditions that also are associated with moderate to severe symptoms of prostatism include use of sedatives or tranquilizers, arthritis, poor health status and transient ischemic attacks. These observations are the initial step in documenting and understanding the various symptoms of prostatism, and its application in clinical practice.

Follow-Up Studies↗
PubMed1991

Multiple pregnancies: risk factors and prognostic variables during induction of ovulation with human menopausal gonadotrophins.

Multiple pregnancies still constitute a major and relatively frequent complication of induction of ovulation by human menopausal gonadotrophins (HMG) despite the increasing sophistication of monitoring techniques. In order to define specific variables which may be associated with multiple pregnancies, we have compared 51 multiple pregnancy cycles to 51 consecutive control singleton pregnancy cycles, following HMG induction of ovulation. The aetiology and classification of anovulation, duration of infertility, total amount of HMG utilized per cycle and the duration of stimulation were not associated with an increase in the rate of multiple pregnancy. Basal serum oestradiol levels and its periovulatory pattern were remarkably similar in the singleton and multiple pregnancy groups. The mean age of the multiple pregnancy group (29.4 +/- 4.4 years) was significantly lower than the mean age of the singleton pregnancy group (31.6 +/- 5.3 years) (P less than 0.05). In the multiple pregnancy group, there were significantly more cycles with intermediate sized (15-17 mm). (P less than 0.002), small sized (12-14 mm). (P less than 0.02) and immature follicles (less than 12 mm) (P less than 0.03), at the time of human chorionic gonadotrophin (HCG) administration, as compared with the singleton pregnancy group. Furthermore, a direct linear correlation was observed between the number of intermediate sized follicles and number of implanted embryos. The presence of intermediate sized follicles at the time of HCG administration after HMG induction of follicular maturation is predictive of, and independently associated with, a higher incidence of multiple pregnancy.

Estradiol↗