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Biomedical subjects

D W Lee

Publications and source records attributed to D W Lee.

At least 145 records · Page 8Linked to original sources

High density cultivation of BSK cells on sintered alumina ceramic foam support.

A perfusion system which utilizes a porous ceramic core has been tested for the cultivation of transformed BHK cells which produce human transferrin. A design is presented in which cells are immobilized within the porous ceramic particle and are fed by continuous perfusion of batch liquid medium. It was found that more than 5 x 10(9) BHK cells could be supported within the 40 mL ceramic matrix, a ten-fold increase in cell density per unit surface area over the standard roller bottle cultures or a five-fold increase in volumetric cell density over suspension cultures. The cell specific productivity of human transferrin was similar to that observed in suspension culture. The system offer the advantages of significant reduction in serum requirements and the potential for scale-up.

Aluminum Oxide↗

The spectral distribution of biologically active solar radiation at Miami, Florida, USA.

The spectral distribution of solar radiation was studied under different sky conditions during a 15-month period in Miami, Florida (USA), and over a latitudinal gradient at solar maximum. Spectroradiometric scans were characterized for total irradiance (300-3000 nm) and the relative energetic and photon contributions of the following wavelength regions: UV-B (300-320 nm); UV-A (320-400 nm); B (400-500 nm); PAR (400-700 nm); R (600-700 nm); and FR (728-732 nm). Notable results include: (i) significantly higher UV-A energy fluxes than currently in use for laboratory experiments involving the biological effects of this bandwidth (values ranged from 33.6 to 55.4 W/m2 in Miami over the year); (ii) marked diurnal shifts in B:R and R:FR, with elevated R:FR values in early morning: (iii) a strong correlation between R:FR and atmospheric water content; and (iv) unusually high PAR values under direct sunlight with cloudy skies (2484 mumol/2 per s).

Cosmic Radiation↗

'Spontaneous'/uremic hypoglycemia is not a distinct entity: substantiation from a literature review.

A review of the literature on 'spontaneous'/uremic hypoglycemia reveals that in only 4 of 36 cases is there no clear explanation for the low blood glucose. In all other cases there were factors in addition to chronic renal failure that could have accounted for hypoglycemia. These factors included states of malnutrition, drugs, and other illnesses. We propose that there is no merit in the term 'spontaneous' hypoglycemia, and that the multifactorial nature of uremic hypoglycemia should be appreciated.

Humans↗

Human follicular fluid contains a follicle-stimulating hormone (FSH) receptor binding inhibitor which has FSH agonist activity, is immunologically similar to FSH, but can be distinguished from FSH.

We have previously reported the presence in human follicular fluid (hFF) of a high (greater than 5000) mol wt FSH receptor binding inhibitor (FSH-BI). This hFF FSH-BI was further purified by removal of material insoluble in acidified acetone (pH 4.1) but soluble in diethyl ether (pH 10.5), followed by molecular sieving through Sephacryl S-100. FSH-BI activity eluted from S-100 with an elution volume similar to that of hFSH, but could be distinguished from hFSH on the basis of a differential sensitivity to acid inactivation. Human FSH was inactivated in acetone at pH 4.1 (1 h, 25 C), whereas hFF FSH-BI retained activity under these conditions. Human FF FSH-BI also demonstrated FSH-like agonist activity, defined as the ability to stimulate basal levels of estradiol synthesis in cultured rat Sertoli cells. Human FSH-BI strongly cross-reacted to a commercially available monoclonal antibody used to measure serum hFSH. Indeed, recovery of FSH immunologic activity was significantly greater (134-fold on a mass basis) after partial purification, indicating that antibody recognition sites were apparently masked in unfractionated hFF. In summary, large mol wt hFSH-BI has been partially purified from hFF and found to be similar in size to pituitary hFSH and to have FSH-like agonist activity in vitro. Although distinguishable from pituitary hFSH on the basis of stability to acid, hFSH-BI appears immunologically related to pituitary hFSH so that measurements of hFSH levels in hFF using immunologic techniques should be interpreted with caution.

Acetone↗

Modulation of free radicals and superoxide dismutases by age and dietary restriction.

Reducing dietary intake has been shown to be the most effective means for modulating aging processes in laboratory rodents. Dietary restriction has also been shown to be a modulator of membrane lipid peroxidation and cytosolic antioxidant status. In the present study, anti-radical action of dietary restriction was investigated further by quantitating the formation of the superoxide radical, hydroxyl radical and hydrogen peroxide by liver microsomes from rats of various ages. The results show that the ad libitum fed group maintained a higher production of superoxide and hydroxyl radicals when compared to the food restricted group of the same age. Hydrogen peroxide formation followed the same trend but was statistically greater only at 3 and 6 months of age. The food restricted group tended to show a higher superoxide dismutase (SOD) activity in both cytosolic and mitochondrial fractions than ad libitum fed controls. These data indicate that the free radical activity observed in the liver microsomes of ad libitum fed rats can be attenuated by dietary restriction, thereby providing a possible biochemical mechanism for its anti-lipoxidative action on membrane lipid peroxidation as reported in an earlier study. This action may in part underlie the life span-prolonging action of food restriction.

Aging↗

Adjuvant treatment of operable stomach cancer with polyadenylic.polyuridylic acid in addition to chemotherapeutic agents: a preliminary report.

A randomized trial of polyadenylic.polyuridylic acid [poly(A).poly(U)] in addition to chemotherapy was undertaken in patients with stomach cancer following curative gastrectomy. They were randomized into a group of 108 patients receiving chemotherapy plus poly(A).poly(U) and a control group of 116 patients receiving chemotherapy alone. Chemotherapy consisted of injections of 5-fluorouracil, 12 mg/kg once weekly and adriamycin, 40 mg/m2 once every 3 weeks, continuously after operation. Poly(A).poly(U) was infused in a 100 mg dose, once a week six times from 5 days after the first injection of chemotherapeutic agents and 6 months later in a half dose similarly. At 55 months after initiation of the trial, the mean follow-up periods were 24 months for both groups. It has been revealed that patients who received the combined treatment postoperatively showed a lesser mortality and lower rate of recurrence, both reflecting significant increases in overall (P less than 0.05) and relapse-free (P less than 0.02) survivals as compared to those who received chemotherapy alone. This effect is more pronounced in patients having moderately advanced lymphnode involvement (N1) than in patients without (N0) or more advanced (N2) involvement. Thus, poly(A).poly(U) appears to be an effective agent when used postoperatively with chemotherapy in stomach cancers.

Aged↗

Mucinous adenocarcinoma of the prostate with endobronchial metastasis.

Endobronchial metastases can manifest clinical symptoms and x-ray findings mimicking a centrally located bronchogenic carcinoma. The authors recently encountered a case of endobronchial metastasis from a mucinous adenocarcinoma of the prostate that was originally diagnosed as a primary bronchogenic carcinoma. The correct diagnosis was made on the basis of the morphologic similarities between the primary prostatic lesion and the lung lesion and was corroborated by immunohistochemical analyses.

Acid Phosphatase↗

Acute anterior wall myocardial infarction secondary to blunt chest trauma--a case report.

Cardiac injuries following nonpenetrating chest trauma have been reported. These include cardiac arrhythmias, septal damage, valve damage, coronary fistula, coronary artery damage, ventricular aneurysm, cardiac rupture, and myocardial infarction. Myocardial infarction as a complication of chest trauma has been reported in very few cases. In this report the authors describe a patient who developed anterior wall myocardial infarction secondary to a blunt chest trauma.

Coronary Vessels↗

Glycosylated human prolactin: alterations in glycosylation pattern modify affinity for lactogen receptor and values in prolactin radioimmunoassay.

The receptor-binding properties of monomeric nonglycosylated human PRL (hPRL), glycosylated hPRL that does not bind to Concanavalin-A-Sepharose (G1-hPRL) and glycosylated hPRL that binds to Concanavalin-A-Sepharose (G2-hPRL) were tested in the lactating rabbit mammary gland RRA for lactogenic hormones. Variations in the glycosylation pattern of G-hPRL altered its receptor-binding properties, suggesting that the site of glycosylation may be proximal to the receptor-binding region. Relative potencies for the displacement of [125I]hPRL by hPRL, G1-hPRL, and G2-hPRL were 100%, 40%, and 26%, respectively. Relative potencies for displacement of [125I]G1-hPRL by hPRL, G1-hPRL, and G2-hPRL were 100%, 44%, and 69%, respectively; however, the displacement curve for G2-hPRL was not parallel to the others. When G2-hPRL was radiolabeled, there was no specific binding to lactogenic receptors. The presence of PRL receptor subtypes and/or kinetic cooperativity was suggested by the complexity of the binding isotherms. The immunoreactivities of the PRLs were tested in a homologous RIA, using polyclonal antiserum. The modification of the glycosylation pattern of hPRL significantly altered the RIA values for PRL. When hPRL was used as the radiotracer, the percent cross-reactivities of hPRL, G1-hPRL, and G2-hPRL were approximately 100%, 23%, and 17%, respectively. When G1-hPRL was used as the radiotracer, the percent cross-reactivities were approximately 100%, 135%, and 54% for hPRL, G1-hPRL, and G2-hPRL; however, the displacement curve for hPRL was not parallel to those of the glycosylated hPRLs. When G2-hPRL was used as the radiotracer, the percent cross-reactivities were approximately 100%, 32%, and 37% for hPRL, G1-hPRL, and G2-hPRL. These data point out that the glycosylation heterogeneity of hPRL is a factor that affects the diagnostic accuracy of hPRL determinations. Specific RIAs for each PRL are needed so that we can have valid and reliable measurements of each PRL isoform and consequently gain a better understanding of PRL's complex biological role.

Animals↗

Differential release of prolactin variants in postpartum and early follicular phase women.

Several molecular forms of immunoreactive human (h) PRL with differences in biological activities have been described. To investigate these differences in PRL secretion, we have characterized the molecular forms of circulating PRL in postpartum women during breastfeeding (n = 5) and sleep (n = 5) and in eumenorrheic women with galactorrhea (n = 5) after TRH stimulation (n = 4), metaclopramide infusion (n = 5), and morphine administration (n = 2). All provocative testing in eumenorrheic women were carried out during the early follicular phase of the menstrual cycle (days 1-5). PRL variants were identified and semiquantitated using sodium dodecyl sulfate-polyacrylamide gel electrophoresis, followed by immunoblotting and autoradiography. Mean basal levels of PRL were significantly elevated in nursing women (P less than 0.01) compared to those in nonlactating postpartum women and women with galactorrhea. The relative proportions of PRL variants [glycosylated PRL with an apparent mol wt of 25K and a nonglycosylated species (hPRL) with an apparent mol wt of 23 K] were similar for all three groups. A third immunoreactive PRL variant with an apparent mol wt of 21K was identified in nonlactating postpartum women. With breastfeeding or sleep, PRL concentrations increased more than 4-fold and were accompanied by a shift toward the lower mol wt, nonglycosylated species. In response to TRH (200 micrograms, iv), PRL levels increased by 493 +/- 86% (mean +/- SE) over basal levels. This acute release of PRL was positively correlated (r = 0.06074; P less than 0.001) with a significant increase in secretion of the hPRL species (P less than 0.05). During metaclopramide infusion, a similar increment in hPRL was observed during acute PRL release. Administration of the opiate agonist morphine was associated with a small increment in PRL release and did not alter the proportions of PRL variants in the circulation. Because glycosylation is a posttranslational step in the processing of PRL, our studies suggest that the acute release of PRL in response to physiological and pharmacological secretagogues may reflect the output of more recently synthesized PRL from the pituitary. The physiological role of the 21K PRL species remains to be determined.

Adult↗

Mechanism of food restriction: protection of cellular homeostasis.

The major difficulty in defining the mechanisms for the action of food restriction relates to its diversity and lack of specificity. In searching for the common factor(s) and commonality involved in such diversified effects, a cellular homeostasis mechanism is proposed. A study initiated in our laboratory strongly indicates that the cellular homeostatic mechanism is seriously compromised by oxidative damage of free radical reaction with aging. Data on mitochondrial hydroperoxide, microsomal cytochrome P-450 breakdown, and reduction of cytosolic antioxidant capacity support the notion. Remarkably, food restriction attenuates all of these age-related changes. It is concluded therefore that food restriction preserves the homeostatic regulatory processes by maintaining the integrity of (i) membrane structure and function, (ii) proper redox state of cellular components, and (iii) detoxification process of xenobiotics.

Aging↗

Identification of low and high molecular weight follicle-stimulating hormone receptor-binding inhibitors in human follicular fluid.

Various fractions of human follicular fluid (FF) were tested for follicle-stimulating hormone (FSH) receptor-binding inhibitory activity, as well as for their ability to form a dansyl derivative previously reported to be associated with FSH receptor-binding inhibitory activity in bovine FF. Pooled human FF was found to inhibit binding of radioiodinated human FSH (125I-hFSH) to its receptor in a concentration-related manner. Fractionation of human FF by sequential ultrafiltration through membranes of calibrated pore size resulted in human FF components of low (500 to 5,000) and high (greater than 5,000) molecular weight, (Mr) respectively. Each of these inhibited 125I-hFSH binding to receptor in a concentration-related manner. Dansylation of the above components revealed the Rf = 0.15 dansyl derivative to be present in unfractionated human FF and in the low (500 to 5,000 Mr), but not the high (greater than 5,000 Mr), component of human FF. These findings are consistent with those previously reported for bovine FF and porcine FF and indicate that human FF contains FSH receptor-binding inhibitors with properties similar to those observed in animal species.

Animals↗

Is anisomycin-induced amnesia for a passive avoidance task in chicks the result of state-dependent learning?

Many studies suggest that protein synthesis is required for formation of long-term memory. To test whether the protein synthesis inhibitor anisomycin (ANI) actually inhibits long-term memory formation or whether apparent amnesia could be attributed to state-dependency, chicks were both trained and tested under the influence of anisomycin (ANI). Two-day-old cockerels were trained in a 1-trial passive avoidance task. Intracerebral injections (10 microliters per hemisphere) of either saline (SAL) or 11.0 mM ANI were made into the medial hyperstriatum ventrale 5 min pretraining and 5 min pretest. The ANI inhibited cerebral protein synthesis by 70-80%, a level necessary to cause amnesia. Chicks that pecked a small bead dipped in methylanthranilate (MeA) and were injected with SAL both pretraining and pretest avoided pecking at test, showing memory for the bitter substance; chicks given ANI pretraining and SAL pretest pecked at the bead during test, which suggests amnesia. However, those given ANI both pretraining and pretest showed marked avoidance at test. Chicks trained to peck at a small bead dipped in water and given injections of either SAL or ANI pretraining and SAL pretest pecked readily at test. However, water-trained chicks given ANI pretest, regardless of pretraining injection, showed significantly higher avoidance at test. We conclude that peck aversion in the ANI-MeA-ANI group was not due to state-dependency but to generalized avoidance induced by pretest ANI.

Amnesia↗

Testosterone metabolism by microsomal cytochrome P-450 in liver of rats treated with some inducers.

1. The stereoselective hydroxylation of testosterone by microsomal cytochrome P-450 and the changes in level of components participated in the microsomal electron transport system were observed in the microsomes induced unique P-450 isozymes. 2. Flavone- and hesperetin-inducible P-450 catalyzed the hydroxylation of testosterone more effectively than other chemicals-inducible ones. 3. The P-450 in all the microsomal preparations tested most rapidly oxidized testosterone to 6 beta-monohydroxy form. 4. Particularly, MC- and BNF-inducible P-450 showed high stereoselectivity on C6-position of testosterone, and PB-, flavone- and hesperetin-inducible one showed that on C2-position of this compound, respectively. 5. This specificity of two flavonoid-inducible P-450 for the formation of 2 alpha- and 2 beta-epimer of monohydroxytestosterone was opposite to each other. 6. The content of P-450 and the activity of NADPH-cytochrome P-450 reductase were high in PB-, MC- and BNF-microsomes, whereas NADH-cytochrome b5 reductase activity was high in two flavonoid-microsomes and the content of cytochrome b5 was not changed except the PB-treated rats. 7. It is suggested that the increasing activities of testosterone hydroxylases in flavonoid-microsomes seems to be closely related to NADH-cytochrome b5 reductase.

Animals↗

Effects of antihistamines on centrifugal rotation-induced analgesia and conditioned flavor aversions.

Centrifugal rotation induces short lasting analgesia, as shown in tail flick tests conducted immediately afterwards, and apparently induces visceral upset that can support aversions for flavors ingested immediately beforehand, as indicated in later preference tests. Two experiments were performed with antihistamines to determine whether the analgesic and visceral effects of rotation were attributable to separate neurochemical systems. In each experiment four groups of rats were defined by factorial combination of UCS (rotation at 150 rpm vs. no rotation) and Drug (antihistamine vs. saline). In Experiment 1 the H1 blocker chlorpheniramine (20 mg/kg, IP) was found to be ineffective against analgesia and to block conditioned flavor aversions (CFAs). In Experiment 2 the H2 blocker cimetidine (100 mg/kg, IP) was found to have a nearly significant attenuating effect on analgesia and to have no effect on CFAs. The data support the idea that analgesia and visceral upset are attributable to separate mechanisms, both of which are activated by the same manipulations.

Analgesia↗

Application of a tapered teflon dilator to percutaneous transluminal coronary angioplasty.

A tapered teflon dilator has been applied to 12 cases of percutaneous transluminal coronary angioplasty (PTCA). The technique was first used to predilate stenoses that could not initially be crossed with low profile over the wire PTCA balloons. In the first five cases, three angioplasties that would have been failures were converted to successes by this method. The dilator was used in place of a balloon catheter as an initial step to assess the ability of a guidewire to cross a lesion to reduce cost in five additional cases. Modification of an existing family of peripheral vascular dilators is described. The method of application of this technique to PTCA is outlined.

Angioplasty, Balloon↗

Application of tapered teflon dilator to PTCA.

A technique using a tapered teflon dilator was applied to percutaneous transluminal coronary angioplasty (PCTA). Seven of 10 cases were successfully dilated by using this technique. These lesions could not be dilated in the usual manner using standard PTCA balloons. This technique converted 7 of 10 failed procedures into technical successes and is the basis of this report.

Angioplasty, Balloon↗