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Biomedical subjects

D Kaufman

Publications and source records attributed to D Kaufman.

At least 109 records · Page 6Linked to original sources

Transforming activity of DNA from rat liver tumors induced by the carcinogen methyl(acetoxymethyl)nitrosamine.

Altered c-Ha-ras genes have been frequently detected in the DNA of spontaneous or chemically induced mouse liver tumors. To determine if ras gene mutation is a frequent event during liver carcinogenesis in rats, we examined the transforming activity of DNA from liver tumors that developed in rats injected with methyl(acetoxymethyl)nitrosamine (DMN-OAc) after a partial hepatectomy. Three weeks after the injection of DMN-OAc, rats were fed a diet containing phenobarbital. This carcinogen acts only on replicating liver cells. Six of eight tumor DNAs induced the transformation of NIH 3T3 cells. The transforming activity was stable upon a second round of transfection, and the transformants were tumorigenic in nude mice. Southern blot analysis of transformant DNAs showed that the transforming activity was not due to the acquisition of a ras (Ha, Ki, or N), neu, myc, A-raf, v-raf, erbA, or erbB gene of rat origin. Several transformants' restriction enzyme sensitivity was analyzed, and their activity indicated that similar transforming sequences were present in at least two tumors and that one tumor contained two different transforming sequences. These results suggest that during hepatocarcinogenesis induced in rats by DMN-OAc, alterations in the ras gene family occur infrequently or not at all and that several different genes (which are not homologous to common oncogenes) become activated and are capable of transforming NIH 3T3 cells.

Animals↗

Basal cell carcinoma: response to systemic chemotherapy for lung carcinoma.

Two patients had regression of basal cell carcinoma while receiving systemic chemotherapy for carcinoma of the lung. The chemotherapeutic agents with some efficacy in basal cell carcinoma are reviewed. Based on our patients and data from the literature, cisplatin appears to be a drug of potential usefulness in some patients with this neoplasm.

Adenocarcinoma↗

AIDS-associated Kaposi's sarcoma: variables associated with survival.

The records of 187 consecutive patients with acquired immunodeficiency syndrome (AIDS)-associated Kaposi's sarcoma were analyzed retrospectively for a number of prognostic variables. In a multivariate analysis, the initial site of disease was found to be related to survival. Initial lesions on the skin of the lower extremities or in the lymph nodes were associated with longer survival (p = 0.005 and p = 0.01, respectively). Higher helper/suppressor T cell ratios were strongly associated with longer survival (p less than 0.0001). Age and serum IgG antibody levels to cytomegalovirus did not appear to correlate. These results suggest that there are different subgroups of patients with AIDS-associated Kaposi's sarcoma, and that the initial site of disease, as well as immunologic parameters, may be useful in prognosis.

Acquired Immunodeficiency Syndrome↗

Continuous intravenous infusions of famotidine maintain high intragastric pH in duodenal ulcer.

Three double blind crossover studies were carried out to assess the ability of primed infusions of famotidine to raise intragastric pH over 24 hours in 12 duodenal ulcer patients. pH was measured continuously using intragastric electrodes and solid state recording devices. The studies compared the effects of placebo, famotidine 10 mg bolus injection iv followed by continuous infusions of 3.2 mg/h and 4 mg/h in random order. Gastric acidity decreased significantly with both dose regimens (p less than 0.0005) but the effects of either dosage were similar. During fasting median pH rose from 1.35 to 7.1 and 7.05 respectively. During the day, when standard meals were taken, median pH rose from 1.30 to 4.3 and 3.65 respectively. Despite continuous infusions the H2-antagonist was less effective during this time. The latter finding raises questions about gastric secretory control during the day when food is eaten.

Adult↗

Gd DTPA. Clinical efficacy.

Both the diagnostic accuracy and sensitivity of the MRI diagnosis of central nervous system neoplasms appear to be improved by the administration of a paramagnetic contrast agent, Gd DTPA.

Brain Neoplasms↗

MR imaging of rat brain glioma: Gd-DTPA versus Gd-DOTA.

The enhancement properties of gadolinium diethylenetriaminepentaacetic acid (DTPA) and gadolinium tetraazacyclododecanetetraacetic acid (DOTA) were compared using a rat glioma model. In vitro analysis included the calculation of T1 relaxivity and determination of characteristic curves. Enhancement of the intracerebral glioma was studied in 23 rats approximately 2 weeks after glioma implantation with Gd-DTPA in 12 rats and Gd-DOTA in 11 rats. Six rats were also studied 1 week after implantation. Gd-DTPA exhibited a slightly greater T1 relaxivity in vitro than Gd-DOTA. Enhancement of the glioma was also greater with Gd-DTPA than with Gd-DOTA (P less than .05).

Animals↗

Multihormonal regulation of insulin-like growth factor-I-related protein in MCF-7 human breast cancer cells.

MCF-7 human breast cancer cells have been studied for hormonal regulation of secretion of an insulin growth factor-I (IGF-I)-related growth factor. 17 beta-Estradiol, which is required for tumorigenesis of the cell line in the nude mouse and which stimulates proliferation in vitro, was able to significantly induce IGF-I secretion at 10(-13) M, with maximal induction at 10(-11) M. Under optimal conditions IGF-I could be induced 4-fold after 4 days. Demonstration of estrogenic stimulations required removal of phenol red, a weak estrogen, from the cell culture medium. In addition to estrogen, insulin, epidermal growth factor, and transforming growth factor alpha induce both cellular proliferation and IGF-I secretion, while growth inhibitory antiestrogens, transforming growth factor beta, and glucocorticoids have the opposite effect. In each case, modulations in IGF-I secretion preceeded effects on cellular proliferation. IGF-I was not regulated by human GH, basic fibroblast growth factor, platelet-derived growth factor, or PRL, none of which affected proliferation rate. Thus, regulation of IGF-I secretion in human breast cancer is controlled by different hormones from those previously reported in human fibroblasts. Regulation of IGF-I by neither estrogen nor antiestrogen was associated with changes in steady-state mRNA levels; thus regulation may occur at a step beyond mRNA. We conclude that IGF-I production is tightly coupled to growth regulation by estrogens, antiestrogens, and other hormones and may contribute to autocrine and/or paracrine growth regulation by these agents in breast cancer.

Breast Neoplasms↗

Effects of age and sex on pattern electroretinograms and visual evoked potentials.

Pattern-electroretinograms (P-ERGs) and visual evoked potentials (VEPs) were simultaneously recorded in 112 normal individuals aged 20-75. Two-sized checks subtending 15' and 31' were used as stimuli. A weighted regression analysis was used to determine which of the variables, sex or age, was significant. The latency of the a and b wave of the P-ERGs showed a progressive increase with age but no difference between sexes. The effect was statistically significant for both 15' and 31' checks. There was no statistically significant aging effect for VEPs elicited by 31' checks. Aging, however, affected N70, P100, and the interpeak interval between b wave to N70 and b wave to P100 for responses to 15' checks. Shorter VEP latencies were noted in females for both 15' and 31' checks. The simultaneous recording of P-ERGs and VEPs has demonstrated that aging is a major variable at the retinal level. The effects on the a and b waves are mostly due to optic changes with aging and only partially to aging changes in the neuronal retinal circuitry. The effect of aging on VEPs is different for different size stimuli. The cause is a random neuronal cell loss in the visual pathways from the optic nerve to the visual cortex as the individual ages. The difference in VEP data between sexes may be related to anatomical size and hormonal influences.

Adult↗

Contrast visual testing in neurovisual diagnosis.

Contrast visual testing (CVT) is a psychophysical visual test of undetermined diagnostic capability in many neurovisual disorders. CVT of 32 controls and 39 patients was compared with the pattern visual evoked response (PVER) from each group. CVT was more sensitive than PVER in detecting visual dysfunction in pseudotumor cerebri and subclinical optic neuritis and showed potential in distinguishing papilledema from pseudopapilledema. PVER was more sensitive than CVT in detecting subclinical visual dysfunction in MS and optic nerve compression. Neither was abnormal in asymptomatic Leber's optic neuropathy. In nonorganic visual loss, CVT data were variable and inconsistent, supporting this diagnosis; PVER was consistently normal. Although in certain disease conditions, each detected subclinical visual dysfunction, neither CVT nor PVER provided specific information leading to an etiologic diagnosis.

Adolescent↗

Successfully treated Hodgkin's disease followed by mycosis fungoides: case report and review of the literature.

We report the case of a 30-year-old man who had Hodgkin's disease of the nodular sclerosing type and subsequently developed mycosis fungoides. The Hodgkin's disease was treated with radiation therapy and chemotherapy, and the patient was in complete remission. Seven years later mycosis fungoides occurred and rapidly became progressive. Autopsy revealed that the mycosis fungoides involved multiple organs without any evidence of Hodgkin's disease. The possible significance of the association of these two diseases is presented.

Adult↗

Simultaneous recording of pattern electroretinography and visual evoked potentials in multiple sclerosis. A method to separate demyelination from axonal damage to the optic nerve.

Pattern electroretinograms (P-ERGs) and visual evoked potentials (VEPs) were recorded in 35 patients with multiple sclerosis and in 35 age-matched normal subjects. Four patterns of abnormalities were noted in the group with multiple sclerosis. The most frequent abnormality consisted of the following: normal P-ERG, delayed P100, and prolonged interpeak interval between the b-wave of the P-ERG and P100 (retinocortical time). This pattern indicates demyelination of the optic nerve. A second pattern consisted of absent P-ERG and absent VEP. This pattern was associated with optic atrophy and/or central scotoma, indicating severe optic nerve axonopathy with retrograde degeneration of ganglion cells. A third pattern consisted of normal P-ERG and absent VEP, suggesting a total block of transmission at the optic nerve. A fourth pattern consisted of present but low-amplitude P-ERG, delayed VEP, and prolonged retinocortical time, indicating a demyelinating process with partial axonal involvement. The concomitant use of P-ERG and VEP results in a better classification of the type and severity of dysfunction affecting the optic nerve. The prognostic value of the four patterns for recovery of visual function is discussed.

Electroretinography↗

The ontogeny of the laminar distribution of beta-adrenergic receptors in the visual cortex of cats, normally reared and dark-reared.

Patterns of distribution of beta 1 and beta 2 adrenergic receptors were examined autoradiographically in slide-mounted sections from the visual cortical areas of 22 developing cat brains, using [125I]iodopindolol as the ligand in combination with displacers specific for beta 1 and beta 2 subtypes of adrenergic receptors. Within visual cortical areas 17 and 18 of adult brains, the density of beta 1 and beta 2 adrenergic receptors was highest in laminae I-III, lowest in lamina IV, and intermediate in laminae V-VI. For beta 1 adrenergic receptors, this laminar distribution was also seen in visual area 19 as well as in the non-visual area 7 that is lateral to area 19. By contrast, the distribution of beta 2 adrenergic receptors varied across cortical areas, such that its density was more homogeneous across the laminae in area 19, and decreased in all laminae in area 7. This pattern of distribution in adult brains was already formed at the beginning of the critical period and was not disturbed by dark-rearing.

Animals↗

Correlation of fine needle aspiration biopsy and CT scanning of parotid masses.

Preoperative evaluation of parotid tumors still poses difficult problems for the head and neck surgeon. The complex anatomy of the parotid space leads to difficulty in localizing these tumors. In addition, physical examination will rarely determine whether a parotid lesion is benign or malignant. High resolution CT scanning with contrast and fine needle aspiration can provide enough preoperative information to enable the surgeon to counsel his patient concerning possible risks and the extent of surgery that may be indicated. We are able to determine tumor location, multiple or bilateral masses, associated adenopathy, and often specific tumor histology. Forty-two parotid aspirates and 26 CT scans were reviewed and correlated with their postoperative pathology specimen. Parotid aspiration cytology was found to be a highly accurate and safe procedure for preoperative determination of parotid pathology. However, the CT scan was specific only in defining the anatomic localization and extent of a parotid mass.

Biopsy, Needle↗