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Biomedical subjects

C Hollander

Publications and source records attributed to C Hollander.

9 recordsLinked to original sources
PubMed1989

The effect of gossypol and 6-aminonicotinamide on tumor cell metabolism: a 31P-magnetic resonance spectroscopic study.

31P-Magnetic resonance spectroscopy has been used to assess the changes in the levels of water-soluble phosphate pools in T47-D breast carcinoma cells induced by the antimitochondrial drugs, gossypol and 6-aminonicotinamide. A decrease in the NTP/Pi ratio occurred after treatment with gossypol. No change in the NTP/Pi ratio occurred on treatment with 6-aminonicotinamide; however, a substantial accumulation of 6-phosphogluconate was observed. Pretreatment of T47-D cells with gossypol prevented the accumulation of 6-phosphogluconate. This facile and non-invasive approach suggests that the oxidative part of the pentose-phosphate shuttle is an important source of reducing equivalents in T47-D cells. This pathway may prove to be a useful target for site-directed drug attack in carcinoma cell lines that require large quantities of NADP for the synthesis of fatty acids and steroids.

6-Aminonicotinamide↗
PubMed1987

Lactic dehydrogenase isozymes, 31P magnetic resonance spectroscopy, and in vitro antimitochondrial tumor toxicity with gossypol and rhodamine-123.

Three compounds that share specific antimitochondrial properties are gossypol, rhodamine-123, and lonidamine. We compare the antiproliferative activities of these drugs against six human cell lines derived from breast (T47-D), pancreas (MiaPaCa, RWP-2), prostate (DU-145), colon (HCT-8), and cervix (HeLa) carcinomas. Tumor cells enriched in cathodal LDH isozymes (LDH4 and LDH5) are significantly more sensitive to gossypol and rhodamine-123. When compared for ability to inhibit growth of human marrow in soft agar, 10 microM gossypol shows little effect on colony formation whereas 10 microM rhodamine-123 completely prevents stem cell growth, suggesting that gossypol may have the most favorable therapeutic index. Within 24 h of drug administration, there is a relative increase in intracellular inorganic phosphate pools and a marked decline in soluble high-energy phosphates in sensitive tumor cells, as measured by 31P magnetic resonance spectroscopy. These studies suggest that specific antimitochondrial agents might be selectively administered on the basis of tumor LDH isozyme content and noninvasively monitored for antiproliferative activity by 31P spectroscopy.

Cell Division↗
PubMed1986

Endocrine-responsive pancreatic carcinoma: steroid binding and cytotoxicity studies in human tumor cell lines.

We have begun to investigate the steroid responsiveness of pancreatic cancer by comparing human (MiaPaCa, Colo-357, RWP-1, RWP-2) and rodent (AR42j) pancreatic tumor cell lines with cultured estrogen receptor-positive breast cancer cells (MCF-7, T47-D). The four human pancreatic tumors contain measurable levels of specific estradiol binding sites with dissociation constants (Kd) that range from 1 to 9 nM, in contrast to the higher-affinity binding sites measured in the breast cancer cells (Kd less than or equal to 1 nM). Growth of one pancreatic tumor line (MiaPaCa) is stimulated 40% above control by exposure to nanomolar concentrations of estradiol, suggesting that the estrogen receptor in these cells is functioning like that in MCF-7 and T47-D cells. Glucocorticoids (dexamethasone, hydrocortisone) and androgen (fluoxymesterone) stimulate proliferation of Colo-357 cells by as much as 30%. Paradoxically, glucocorticoids inhibit AR42j cells to less than 50% of control growth. Micromolar exposures of estrogen (17 beta-estradiol), antiestrogen (tamoxifen), antiandrogen (dehydroxyflutamide), progestins (progesterone, R5020, medroxyprogesterone acetate), and inhibitors of steroid-metabolizing enzymes (17 beta-N,N-diethylcarbamyl-4-methyl-4-aza-5 alpha-androstan-3-one, danazol) impair growth of these pancreatic tumors to varying degrees, and with little relationship to estrogen receptor content. In general, progestins are slightly more growth inhibiting to these pancreatic tumor lines than the other endocrine agents tested, including tamoxifen. Only the RWP-2 cells appear completely resistant to steroidal therapy, showing less than 25% growth inhibition with exposure to therapeutic concentrations (less than or equal to 2.5 microM) of these agents. Colo-357, MiaPaCa, and AR42j cells are most responsive to these endocrine agents, and their overall pattern of sensitivity suggests that the steroid-dependent growth-inhibitory mechanisms of some pancreatic carcinomas may involve both receptor antagonism and direct inhibition of steroidal oxidoreductases. 17 beta-N,N-Diethylcarbamyl-4-methyl-4-aza-5 alpha-androstan-3-one, a potent inhibitor of 5 alpha-reductase with minimal affinity for androgen receptor, inhibits growth of Colo-357 cells to less than 40% of control and also inhibits AR42j and MiaPaCa cells. Dehydroxyflutamide, a potent androgen receptor antagonist with no direct influence on 5 alpha-reductase activity, inhibits growth of MiaPaCa and AR42j cells but has no affect on Colo-357 growth.(ABSTRACT TRUNCATED AT 400 WORDS)

Aminoglutethimide↗
PubMed1985

Amorphic lenses: a mobility aid for patients with retinitis pigmentosa.

An amorphic lens, designed by William Feinbloom, was tested on 69 patients with retinitis pigmentosa. The results showed that one-half of the patients experienced immediate improvement in mobility and one-third of the patients fitted with the amorphic lens reported (after wearing the lenses for 2 weeks) improved mobility compared to their mobility before using the lens.

Equipment Design↗
PubMed1976

Use of noninvasive methods in evaluation of left ventricular performance in coronary artery disease. II: Change in systolic time intervals after coronary artery bypass in patients with stable angina.

Serial recording of systolic time intervals (STI) was used to assess changes in left ventricular (LV) function in 92 patients with stable angina undergoing coronary angiography and LV cineangiography. On the basis of angiography, patients were placed in the following study groups: mild or absent coronary artery disease group -21 patients with less than 70 per cent occlusion of all coronary arteries, considered to have non-significant coronary artery disease and not needing bypass surgery; surgical bypass group-52 patients with evidence of significant (less than 70%) obstruction of at least one coronary artery who underwent myocardial revascularization; and medical group-19 patients with evidence of significant coronary artery disease not undergoing bypass surgery. Measured STI, corrected for heart rate and sex, were expressed as indices. No significant differences were noted in the mean STI from the time of initial evaluation to second evaluation 3 to 6 months later in either the mold or absent coronary artery disease patients or the medical group. In the surgical bypass group, however, serial studies at initial angiographic evaulation and 3 to 6 months after bypass surgery showed a shortened pre-ejection period (PEP) from 150 +/- 20 to 142 +/- 16 mn (P less than 0-001), prolonged left ventricular ejection time (LVET) from 396 +/- 21 to 409 +/- 14 ms (P less than 0-02), and decreased PEP/LVET from 0-45 +/- 0-11 to 0-04 +/- 0-07 (P less than 0-02). Paired data analysis of the three groups also showed a significant change only within the surgical bypass group from initial to find study, with a shortened PEP (P less than 0-002), prolonged LVET (P less than 0-001), and decreased PEP/LVET (P less than 0-001). These data suggest improvement in LV function in patients with significant coronary artery disease within a few months of myocardial revascularization, without demonstrable change in STI in those patients with coronary artery disease not subjected to revascularization.

Adult↗
PubMed1975

The use of noninvasive methods in the evaluation of left ventricular performance in coronary artery disease. I. Relation of systolic time intervals to angiographic assessment of coronary artery disease severity.

Determination of left ventricular performance by external STI was evaluated in 113 patients with possible coronary artery disease undergoing selective coronary artery disease undergoing selective coronary arteriography and left ventriculography. Angiographically determined significant coronary artery disease was considered as 70 per cent obstruction of a coronary vessel. PEPI and PEP/LVET increased with increasing severity of coronary artery disease. LVETI decreased with increasing coronary artery involvement. Presence of prior myocardial infarction or clinically apparent congestive heart failure did not significantly alter mean STI values when groups were compared according to severity of coronary artery disease. LVETI was significantly less for patients with three-vessel coronary artery disease than for those with no significant disease; PEPI and PEP/LVET were significantly greater in those with two- or three-vessel disease than in those without significant disease. Angiographically determined LVEF correlated directly with LVETI and inversely with PEPI and PEP/LVET. Abnormal left ventricular wall motion was associated with decreased LVETI and increased PEPI and PEP/LVET. LVEDP was not significantly different in any of the groups. These findings indicate that externally determined systolic time intervals reflect abnormalities in left ventricular performance which in turn appear more pronounced with increasingly extensive coronary artery disease.

Adult↗
PubMed1975

The effect of iodized oil on the TSH response to TRH in endemic goiter patients.

The TSH and T3 response to synthetic TRH was evaluated in 4 groups of patients: normal controls and goitrous subjects from the urban area of Sao Paulo (urinary iodine excretion: 172.2 +/- 48.3 mug I/g creatinine) and nongoitrous and goitrous subjects from the endemic areas of Sao Bento (urinary iodine excretion: 53.8 +/- 17.1 mug I/g). Plasma T4 and T3 were within our normal range in all groups of patients. The mean plasma TSH was significantly higher (5.2 +/- 3.3 muU/ml) in goitrous subjects living in Sao Bento as compared to normal control groups both in urban or endemic areas, and after TRH these patients had an exaggerated and sustained TSH response with a significantly higher peak level (21.1 +/- 7.9 muU/ml). T3 concentration rose in all subjects following TRH and all patients from the Sao Bento endemic areas had a significantly higher proportionate increase in plasma T3 at 120 min. After an injection of iodized oil basal plasma TSH returned to the normal range in the goitrous subjects from Sao Bento. The mean peak TSH response to TRH was 9.1 +/- 3.8 muU/ml at 3 months after the iodized oil injection, and only at 6 months after the iodized oil TSH response was significantly reduced (peak level: 6.1 +/- 2.4 muU/ml). It is confirmed that plasma TSH levels are increased in endemic goitrous patients but not in normal controls living in the same endemic area and it is suggested that the pituitary threshold for inhibition of secretion of TSH by T4 and T3 has been reset in these goitrous subjects to achieve a persistently higher secretion rate of TSH.

Brazil↗