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M Goldenberg

Publications and source records attributed to M Goldenberg.

At least 91 records · Page 5Linked to original sources

Angiogenesis and blood-brain barrier breakdown modulate CT contrast enhancement: an experimental study in a rabbit brain-tumor model.

Because of the crucial role played by tumor neovascularization in contrast enhancement, we studied the CT imaging findings in a transplantable rabbit brain tumor, the VX2 carcinoma that induces angiogenesis and the breakdown of blood-brain barrier associated with contrast enhancement. Tumor detection by contrast enhancement followed the peak of angiogenesis. Inhibition of angiogenesis, by copper depletion and penicillamine, led to avascular tumors that lack contrast enhancement. Furthermore, there was no contrast enhancement in brain adjacent to the tumor of normocupremic rabbits or within the hypocupremic tumor, despite the breakdown of the blood-brain barrier, without the concomitant presence of angiogenesis. We conclude that contrast enhancement of intracranial tumors is dependent primarily on the proliferation of the microvasculature.

Animals↗

Programmed oocyte retrieval: clinical and biological effects of oral contraceptives administered before in vitro fertilization.

We have prospectively compared two regimens of suppression of the hypothalamic-pituitary-ovarian axis by oral contraceptives (OCs) for 15 or 30 days and two ovarian stimulation protocols. The latent phase, which represents a period of ovarian insensitivity, was prolonged and directly correlated to the duration of suppression. Thirty days' suppression, compared with 15 days', resulted in the cancellation of more cycles and a lower fertilization and pregnancy percentage. No significant increase in either serum progesterone or luteinizing hormone was noted in suppressed cycles. It is concluded that if programming is desired, OCs should be used for the shortest period possible. The variation in the length of the follicular phase indicates that there is a different 'fixed' day for retrieval for each suppression-stimulation protocol and this day should be established prospectively.

Adult↗

Synthesis and properties of novel psoralen derivatives.

We have synthesized a set of new trimethylpsoralen derivatives that are characterized by a chain extending from the 4'-position of the furan ring and linked to this ring by an aminomethylene group. The nature of the side chain can be varied widely. In these derivatives, the chains contain either amino or ethylene oxide units for enhanced water solubility and allow the introduction of a thiol or amine group to nucleic acids. These compounds represent the first set of thiolated psoralen derivatives, and their usefulness is demonstrated in several nucleic acid cross-linking experiments. The reagents can be used to create both intraduplex reversible cross-links between the two single-strand partners in a DNA double helix and interduplex reversible cross-links between two DNA double helices.

Cross-Linking Reagents↗

Protocols for induction of ovulation. The concept of programmed cycles.

Programmed oocyte retrieval which includes suppression of the hypothalamic-pituitary-ovarian axis by oral contraceptives or GnRH analogue and predetermined ("fixed") day for ovum pick-up has been demonstrated to yield a pregnancy rate that is comparable to that achieved by the conventional individualized approach to follicular maturation. We have prospectively compared two regimens of suppression (the pill and GnRH analogue) followed by two ovarian stimulation protocols (clomiphene citrate + human menopausal gonadotropin [CC + hMG] and pure follicle-stimulating hormone + human menopausal gonadotropin [pure FSH + hMG]). Sixteen patients were studied in each group. It was found that the latent phase, which represents a period of ovarian insensitivity, was prolonged and directly correlated to the duration of suppression, and that suppression with the GnRH analogue was associated with a shorter latent phase than that with the pill. Suppression with the pill for 30 days compared with 15 days resulted in a greater cancellation of laparoscopic oocyte retrieval, a lower fertilization rate, and a lower pregnancy rate. The numbers of oocytes recovered, fertilized, and cleaved were similar in both stimulation protocols. The use of the GnRH analogue for 30 days compared with 15 days was associated with a lower pregnancy rate, even though the number of oocytes that were recovered and fertilized were similar. Ovarian stimulation with pure FSH + hMG resulted in a shorter latent phase than did stimulation with CC + hMG, but the results of treatment with both protocols were similar. It is concluded that both the pill and GnRH analogue are acceptable means of manipulating the cycle and the day of oocyte retrieval. However, they should be used for the shortest periods possible because prolonged use is associated with some unwarranted effects. For each suppression-stimulation protocol there seems to be a different fixed day for retrieval that should be established prospectively.

Chorionic Gonadotropin↗

Rescue of menotrophin cycles prone to develop ovarian hyperstimulation.

In an attempt to prevent the loss of 'overstimulated cycles' associated with human menopausal gonadotrophin (hMG)-induced ovulation, oestradiol levels and ovarian follicular state were monitored in 12 women with 'overstimulated cycles' after withholding hMG for several days. Human chorionic gonadotrophin (hCG) was administered when oestradiol levels were less than or equal to 1700 pg/ml and the leading follicles between 17 and 22 mm in diameter. During the withholding period follicular growth continued in all patients, while oestradiol levels declined in all but three. These three patients conceived. Ovulation was observed in six additional women. Ovarian hyperstimulation did not occur in any of the 12 patients. We conclude that a rescue of 'overstimulated cycles' is sometimes possible. Conception seems to depend on a continuing rise of E2 levels and early detection of 'overstimulation'.

Chorionic Gonadotropin↗

Changing pituitary reactivity to follicle-stimulating hormone and luteinizing hormone-releasing hormone after induced ovulatory cycles and after anovulation in patients with polycystic ovarian disease.

Pituitary reactivity to GnRH, characteristic of polycystic ovarian disease (PCOD), has been attributed both to a primary ovarian cause and to hypothalamic-pituitary dysfunction. If the heightened pituitary reactivity characteristic of PCOD patients is secondary to chronic anovulation, ovulatory cycles should produce changes in the LH to FSH ratio and reduce the augmented response to GnRH. In a randomized cross-over study of 10 women with PCOD, GnRH (100 micrograms) was injected iv on the fifth day of 2 consecutive cycles, 1 of them following anovulation and progesterone withdrawal bleeding and the other following an induced ovulatory cycle. Mean basal plasma 17 beta-estradiol, progesterone, and FSH levels were similar after ovulatory and anovulatory cycles. However, mean basal serum testosterone (P less than 0.05) and LH (P less than 0.01) levels were significantly lower, as were LH levels 30, 60, and 90 min (P less than 0.01) and FSH levels 60 and 90 min (P less than 0.05) after GnRH injection, after an ovulatory cycle than after an anovulatory cycle. The pituitary response to GnRH in those PCOD patients, therefore, was more normal after an ovulatory cycle than after an anovulatory cycle. We conclude that the heightened pituitary reactivity characteristic of PCOD patients is associated with chronic anovulation.

Adult↗

Poststroke depression and lesion location. An attempted replication.

Recent evidence suggests that poststroke depression is associated with the location of the brain infarct, proximity to the frontal pole being associated with greater depression following left hemisphere injury, and an opposite relationship being seen with injury to the right hemisphere. This study was designed to replicate and extend previous investigation of this issue. Depression was assessed following recent stroke in patients with localized right (n = 16) or left (n = 19) hemisphere lesions. No overall differences between these groups were found on several measures of depression. Although there appeared to be a negative linear relationship between severity of depression and distance of the lesion from the frontal pole in left hemisphere patients, this association failed to attain statistical significance. A curvilinear relationship was evident in right hemisphere patients, with anterior and posterior lesions associated with high depression scores. These data support the notion that lesion location is associated with the severity of poststroke depression, although the nature of this association may be more complex than has previously been suggested.

Aged↗

Pharmacological effects of non-steroidal antiinflammatory agents on prostaglandin and leukotriene synthesis in mouse peritoneal macrophages.

Resident mouse peritoneal macrophages, exposed to zymosan, synthesized and released products of both the cyclooxygenase and lipoxygenase pathways. The effects of various non-steroidal antiinflammatory agents were evaluated for their abilities to inhibit zymosan-stimulated prostaglandin E2 (PGE2) and leukotriene C4 (LTC4) synthesis. The order of potencies to inhibit PGE2 synthesis and release was: indomethacin greater than or equal to sulindac sulfide greater than ibuprofen greater than or equal to aspirin greater than 3-amino-1-[3-(trifluoromethyl)-phenyl]-2-pyrazoline (BW755C) greater than benoxaprofen greater than or equal to nordihydroguaiaretic acid (NDGA) greater than 5,8,11-eicosatriynoic acid (ETYA). BW755C and ETYA also inhibited zymosan-stimulated LTC4 production. None of the compounds tested showed selective inhibition of lipoxygenase products.

4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyraz↗

Evidence for two sources of arachidonic acid for oxidative metabolism by mouse peritoneal macrophages.

The products of arachidonic acid oxygenations by resident mouse peritoneal macrophages have been found to depend upon the nature of the stimulus. For example, soluble membrane-mediated inflammatory stimuli such as phorbol myristate acetate and lipopolysaccharide stimulated the formation of prostaglandin E2 via the cyclooxygenase pathway. In contrast, zymosan, a particulate, phagocytozable inflammatory mediator stimulated leukotrienes C4 and B4 synthesis via the lipoxygenase pathway in addition to stimulating prostaglandin E2 synthesis. Thus, the release of leukotrienes is not necessarily linked to the release of prostaglandins in a cell that has the enzymatic capability of producing both mediators. This suggests that the prostaglandin synthetase system can obtain substrate arachidonic acid from a source different from that for leukotriene synthesis.

Animals↗

Site-directed psoralen crosslinking of DNA.

A technique has been developed for placing site-specific crosslinks into DNA by using a psoralen derivative containing a sulfhydryl group. Plasmid pBR322 was nicked at the unique BamHI restriction site, and mercurated pyrimidines were introduced by nick-translation. Then the psoralen was specifically directed to this site in the dark through a Hg-S linkage prior to irradiation to form a crosslink. The location of interstrand cross-links was examined by electron microscopy of Pst I-cut molecules and found to be at or near the BamHI site.

Cross-Linking Reagents↗

Use of fluorescent probes that form intramolecular excimers to monitor structural changes in model and biological membranes.

1,3-dipyrenylpropane (PC3P) and bis(4-biphenylmethyl)ether, two molecules that form intramolecular excimers, were embedded in phospholipid vesicles and biological membranes to monitor dynamic properties of membrane lipids. Excimer formation was evaluated from determinations of excimer to monomer emission intensity ratios (ID/IM). ID/IM values of PC3P and bis(4-biphenylmethyl)ether were reduced when cholesterol was added to egg lecithin vesicles. PC3P was sensitive to the temperature-induced crystalline to liquid-crystalline phase transition in dimyristoyl phosphatidylcholine vesicles. For studies of cellular membranes, membranes, PC3P was used exclusively, because of the fluorescence of tryptophan residues of membrane proteins interferes with the responses bis(4-biphenylmethyl)ether. Microviscosities of membrane interiors were calculated from standard curves of IM/ID plotted against solvent viscosity. Microviscosity values of egg lecithin vesicles and biological membranes, especially those obtained with PC3P, were more than an order of magnitude lower than values obtained by other techniques. We concluded that the intramolecular process leading to the formation of the excimer is influenced differently in isotropic solvents than in anisotropic environments, such as lipid bilayers. Although distinguishable ID/IM ratios can be obtained for different biological membranes (mitochondrial, microsomal, and plasma membranes were studied), this parameter may be phenomenological and not simply related to membrane microviscosity. As such, fluorescent probes that form intramolecular excimers are of value in making qualitative comparisons of different membranes and in studying the relative effects of physical changes and chemical agents on membrane structure. These probes may also be valuable for studying structural anisotropy of biological membranes.

Animals↗

Jugular bulb diverticula in medial petrous bone.

Upward extension or diverticulum of the jugular bulb is rare. Most often, it protrudes into the middle ear. Three patients are reported in whom direct superior extension from the medial portion of the jugular bulb resulted in a defect in the medial part of the petrous bone. In this position, a jugular bulb diverticulum relates directly to the posterior wall of the internal auditory canal. The distinctive radiographic characteristics of this entity obviate unnecessary investigation and surgery. Encroachment on the internal auditory canal may possibly contribute to neurosensory hearing deficit.

Aged↗

Computed tomography of the enlarged cisterna magna.

The unusual appearance of the large cisterna magna on computed tomography is presented and the radiographic signs are reviewed and correlated. This entity may be confused with a variety of other lesions. Awareness of such developmental anomalies may obviate the need for angiography and pneumoencephalography in selected cases.

Adolescent↗

More causes of button sequestrum.

Two cases illustrating the association of button sequestra with Paget's disease and multiple myeloma are presented, followed by a brief review of the roentgenologic skull manifestations of these diseases. The number of conditions having button sequestra now stands at thirteen. The sign has no specific diagnostic significance.

Aged↗