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Biomedical subjects

D S Lin

Publications and source records attributed to D S Lin.

At least 37 records · Page 2Linked to original sources

Differential mobilization of fatty acids from adipose tissue.

Are the different fatty acids mobilized into plasma in proportion to their concentrations in adipose tissue triglyceride? To answer this question, we fed weaning rabbits a special diet to label the fat stores with a variety of dietary fatty acids. The release of adipose tissue fatty acids into the plasma was then induced by ACTH-stimulated lipolysis. The compositions of the resulting plasma free fatty acids and of the adipose tissue triglyceride were then compared. Plasma free fatty acids increased from 625 mumol/L at baseline to 2938 mumol/L after ACTH and represented fatty acids released from adipose tissue. The relative mobilization of these fatty acids from adipose tissue was defined as the ratio between their percentage in the plasma free fatty acid fraction to their percentage in adipose tissue triglyceride. For the 24 fatty acids examined, the relative mobilization ranged from 0.11 for 22:1 n-11 to 5.06 for 20:5 n-3, a 46-fold difference. Relative mobilization correlated positively with unsaturation and negatively with chain length. The relative mobilization for essential fatty acids was in the order of 20:5 n-3 > 20:4 n-6 > 18:3 n-3 > 22:6 n-3 > 18:2 n-6. Saturated fatty acids, along with oleic acid, were much less well mobilized than the entire group of polyunsaturated fatty acids. Our data indicate that the mobilization of fatty acids into plasma was not proportional to their content in adipose tissue, but rather was influenced by their molecular structure. Eicosapentaenoic acid 20:5 n-3 (EPA), and arachidonic acid 20:4 n-6, precursors of two different prostaglandins, were the fatty acids with the highest mobilization into the plasma.

Adipose Tissue↗

Absence of protective resistance to homologous challenge infections in jirds with chronic, amicrofilaremic infections of Brugia pahangi.

Most jirds (Meriones unguiculatus) with chronic Brugia pahangi infections remain microfilaremic, develop a hyporesponsive state, and are susceptible to reinfection. Although few, some jirds become amicrofilaremic or fail to develop a microfilaremia. The hypothesis that chronically infected, amicrofilaremic jirds may be resistant to reinfection was tested. Twenty-four chronically infected amicrofilaremic jirds, with or without circulating antigen, were inoculated subcutaneously with 75 B. pahangi third-stage larvae (L3). Necropsies were performed 25 days postinoculation, and challenge populations were separated from existing worms by size. Similar inoculations and necropsies were performed on groups of chronically infected microfilaremic jirds and uninfected jirds. Based on worm recoveries, jirds with occult infections were not resistant to reinfection. An anamnestic antibody response to extracts of L3 or microfilariae (mf) was not seen, nor were antibodies to the surface of L3 or mf. The data indicate that a susceptible state is maintained in this model of lymphatic filariasis in the absence of circulating mf.

Animals↗

The lipids of slugs and snails: evolution, diet and biosynthesis.

There is a considerable gap in current knowledge of the lipid composition of snails and slugs, both of which belong to the phylum Mollusca. We have therefore analyzed the sterol and fatty acid compositions of three species of slugs and three species of snails. The sterols of slugs included eight different sterols: cholesterol contributed 76-85% of the total sterols, brassicasterol accounted for 4-13%; other sterols we identified were lathosterol, 24-methylene cholesterol, campesterol, stigmasterol, sitosterol and sitostanol. In contrast, snails contained two additional sterols, desmosterol and cholestanol. Of the polyunsaturated fatty acids in slugs, linoleic (18:2n-6) and arachidonic acids (20:4n-6) were the major n-6 fatty acids, while linoleic (18:3n-3) and eicosapentaenoic acids (20:5n-3) were the predominant n-3 fatty acids. Docosahexaenoic acid (22:6n-3), the end product in the n-3 fatty acid synthetic pathway and an important membrane fatty acid of mammals, fish and birds, was absent in both slugs and snails. However, the analogous product of n-6 fatty acid synthesis, 22:5n-6, was found in both snails and slugs. This raises speculation about preference for n-6 fatty acid synthesis in these species. Our data show the unique sterol and fatty acid compositions of slugs and snails, as well as similarities and differences in sterol composition between the two. The results between the two land mollusks are contrasted with those of marine mollusks, such as oysters, clams and scallops.

Animals↗

Effect of dietary N-3 fatty acids upon the phospholipid molecular species of the monkey retina.

PURPOSE: To characterize the molecular species composition of ethanolamine glycerophospholipids (EGP) in the primate retina and to examine the effects of different dietary fats, the authors fed rhesus monkeys diets containing widely ranging amounts of n-3 fatty acids. METHODS: From birth, infant monkeys were fed either a control soybean oil diet, containing 8% of total fatty acids as 18:3 (n-3), or a safflower oil-based n-3 fatty acid deficient diet containing < 0.4% 18:3 (n-3). A subset of the n-3 deficient group was later repleted with 1.6% ethyl docosahexaenoate, 22:6 (n-3), starting at 10 months of age. Tissues were taken from all monkeys upon termination at 21 to 51 months of age. The diacyl, alkenylacyl, and alkylacyl EGPs were quantitated by high-pressure liquid chromatography (HPLC). RESULTS: Twenty-eight molecular species were identified in the retina of control monkeys. Ether phospholipids comprised 36% of the retinal ethanolamine glycerophospholipids. Species containing polyunsaturated fatty acids in both the sn-1 and sn-2 positions (dipolyenes) were present only in the diacyl subclass and comprised 16% of the total species. Species having n-3 fatty acids in the sn-2 position contributed 59%, 36%, and 70% of total species in the diacyl, alkenylacyl, and alkylacyl subclasses, respectively. In the molecular species of the n-3 fatty acid deficient monkeys, the major change was the loss of most of the 18:0-22:6(n-3) species and its partial replacement with 18:0-22:5(n-6). In contrast, the species 18:1-22:6(n-3) decreased only slightly, from 6.2% to 4.8% of total diacyl species. Although the total concentration of dipolyenes (15% to 20% of the total species) was not affected by diet, their fatty acid compositions were changed drastically. The dipolyene species 22:6(n-3)-22:6(n-3) nearly disappeared in the n-3 deficient monkeys. Concomitantly, two new species, 22:5(n-6)-22:6(n-3) and 22:5(n-6)-22:5(n-6), appeared at 2.6% and 2.0%, respectively. Deficient monkeys given the ethyl ester of 22:6(n-3) in the diet recovered to a near-normal molecular species composition, except in the ether lipids, in which 16:0-20:4 remained low. CONCLUSION: Diets of differing n-3 fatty acid content had profound qualitative and quantitative effects on the molecular species of retinal phospholipids, and the replacement of 22:6(n-3) by 22:5(n-6) in the retinas of n-3 deficient monkeys was asymmetric and functionally incomplete.

Animals↗

Spinal lymphosarcoma and disseminated mastocytoma associated with feline immunodeficiency virus infection in a cat.

The course of naturally acquired infection with feline immunodeficiency virus was monitored in a cat over an 18-month period after diagnosis. The cat was admitted with diarrhea, poor body condition, a bite wound abscess, gingivitis, chronic fever, and splenomegaly. The cat's condition improved after splenectomy and remained stable for approximately 15 months, then began to deteriorate, as gingivitis, polyuria, polydipsia, pyrexia, multiple cutaneous masses, and hind limb paresis developed. The in vitro response of the cat's lymphocytes to mitogens was suppressed, and absolute lymphocyte counts were low. Spinal lymphosarcoma, disseminated mastocytoma, and presumptive diabetes mellitus were diagnosed after euthanasia. Decreased immune surveillance associated with feline immunodeficiency virus-related immunosuppression possibly played a role in the development of neoplastic disease in this cat.

Animals↗

Detection of tumor necrosis factor activity in the supernatants of feline macrophages and lymphocytes.

Using tumor necrosis factor (TNF)-sensitive L929 cells, TNF-like activity was assayed in the supernatants of feline macrophage and lymphocyte cultures. Macrophages were separated from thioglycollate-elicited peritoneal cells. Lymphocytes were purified from peripheral blood and were then stimulated with calcium ionophore A23187 and phorbol myristate acetate. Lymphocyte stimulators alone did not have cytotoxicity against L929 cells. Based on the facts that cytotoxicity decreased with increasing dilutions of supernatant and that this cytotoxic activity could be blocked by antibody to human TNF, the activity detected in the supernatants of the feline macrophages and lymphocytes was likely due to feline TNF-alpha or -beta.

Animals↗

Are dietary saturated, monounsaturated, and polyunsaturated fatty acids deposited to the same extent in adipose tissue of rabbits?

The objective of this study was to determine the effect that different dietary fatty acids would have on the fatty acid composition of adipose tissue. Thirty adult rabbits were starved 3-4 wk to deplete adipose tissue stores. They were then refed five different fats (linseed, rapeseed, cocoa butter, palm, and safflower oils) to regain initial body weights. The fatty acids of the adipose tissue, in general, reflected the diet. Positive correlations between the amount of the five commonly consumed fatty acids (palmitic, stearic, oleic, linoleic, and linolenic acids) in the diet and their deposition into the adipose tissue were observed. All polyunsaturated and monounsaturated fatty acids were well incorporated into the adipose tissue, even linolenic acid. The deposition of dietary saturated fatty acids (ie stearic acid) was limited. Our data showed that the fatty acids of dietary fats may greatly affect adipose fatty acid composition. Thus, adipose stores of essential fatty acids can be greatly augmented by diet.

Adipose Tissue↗

Temporal changes in myocardial uptake on serial bone scans in two cases of presumed senile cardiac amyloidosis.

Two unusual examples of cardiac uptake in elderly patients who had received serial bone scans, one with a "waxing" and the other with a "waning" pattern of myocardial tracer uptake, are presented. An apparent temporal discordance between echocardiographic and scintigraphic findings is noted. Neither of the two patients had clinical, electrocardiographic, or other laboratory evidence of old or new myocardial infarction. Possible causes for the temporal changes are described. Presumptive diagnoses of senile cardiac amyloidosis were made based on clinical findings, noninvasive imaging, and comparison with a historic cohort at the Veterans Administration Medical Center in Houston.

Aged↗

Unique lipids of primate spermatozoa: desmosterol and docosahexaenoic acid.

Spermatozoa represent a tissue readily accessible for study after various exogenous perturbations. To characterize the lipid composition of monkey sperm and to establish a baseline from which dietary or pharmaceutical influences may then be evaluated, we collected semen samples from five rhesus monkeys by electroejaculation and analyzed the sperm for sterols, fatty acid composition, and the molecular species of the ethanolamine glycerophospholipids. Two sterols were identified: cholesterol, 41%, and desmosterol, 59% of total sterols. Desmosterol was found only in the free form. Cholesterol existed in three different forms: free, 60%; esterified, 20%; and sulfated, 20%. Docosahexaenoic acid (22:6, DHA) was almost the only n-3 fatty acid in sperm phospholipids, 24% of the total fatty acids. DHA was present mainly in phosphatidylcholine and phosphatidylethanolamine. Oleic and palmitic acids were the predominant monounsaturated and saturated fatty acids. The ethanolamine glycerophospholipids were separated into three subclasses: diacyl 49%, alkenylacyl 43%, and alkylacyl 8%. Thirteen molecular species were identified and quantified. The sn-1 position of these molecular species contained exclusively 16:0, 18:0, or 18:1. The sn-2 position contained n-3, n-6, and n-9, as well as saturated fatty acids. The molecular species having n-3 fatty acids in the sn-2 position contributed 43, 73, and 100% of the total in the diacyl, alkenylacyl, and alkylacyl subclasses, respectively. The presence of the unusual sterol, desmosterol, a cholesterol precursor not found in measurable quantities in any other tissue suggests an important functional and structural role for desmosterol in spermatozoa. The other unique lipids, cholesterol sulfate and the n-3 docosahexaenoic acid, may also have a significant role in the function of spermatozoa.

Animals↗

Antibody responses to Toxoplasma gondii antigens in aqueous and cerebrospinal fluids of cats infected with T. gondii and FIV.

Antibodies to antigens of Toxoplasma gondii were measured in the aqueous and cerebrospinal fluid (CSF) of 16 specific-pathogen free kittens experimentally infected with feline immunodeficiency virus (FIV), T. gondii, or both pathogens. The results indicated that all cats infected with T. gondii had antibody responses to antigens of T. gondii in both aqueous fluids and CSF. Co-infection with FIV did not affect antibody levels. Aqueous fluids from eyes of cats with toxoplasmic retinochoroiditis did not necessarily have higher antibody levels than those from eyes without lesions. Antibodies to T. gondii were also detected in the CSF of two cats from whose brains no parasites were isolated by in vivo mouse inoculation. Total IgG did not increase significantly in the aqueous fluids and CSF of cats infected with T. gondii whether or not they were also infected with FIV.

Animals↗

Change in interleukin 2 production by lymphocytes during maturation of young cats.

Lymphocytes from four specific-pathogen free cats were tested for their interleukin 2 activity every week beginning when the cats were 12 weeks old and ending when they were 26 weeks old. Lymphocytes from cats > or = 20 weeks old released significantly more interleukin 2 than those obtained from these cats at earlier ages when stimulated with calcium ionophore A23187 and phorbol myristate acetate. The change of interleukin 2 levels with maturation of young cats may represent an important difference in their level of defense to infections with various pathogens.

Aging↗

Feline immune system.

Immunological features of feline lymphocytes, immunoglobulins, monocytes/macrophages, cytokines, major histocompatibility complex and delayed-type hypersensitivity are reviewed. Attention is given to the comparison of the feline immune system with the immune systems of humans and other animals. Also presented is information on the modification of feline immunity by pathogens.

Animals↗

Macrophage functions in cats experimentally infected with feline immunodeficiency virus and Toxoplasma gondii.

It was suspected that feline immunodeficiency virus (FIV) infection would affect the function of feline macrophages, and that the concomitant infection of cats with FIV and Toxoplasma gondii would cause even greater changes in macrophage function. Sixteen specific-pathogen-free kittens, four per group, were infected either with FIV, T. gondii, both pathogens, or neither pathogen. After the cats had been infected with FIV for 14 weeks (8 weeks after T. gondii infection), peritoneal macrophages were collected. Some macrophages were stimulated with lipopolysaccharide and supernatants were collected for the measurement of interleukin-1 production. Other macrophages were infected with T. gondii in a microbiocidal assay. Peritoneal macrophages from cats infected with FIV had decreased interleukin-1 secretion and increased antimicrobial activity. Co-infection with T. gondii apparently had no effect on these modifications of macrophage activity. Thus, acute FIV infection alone caused significant changes in macrophage functions that were not affected by concomitant T. gondii infection.

Animals↗

Toxoplasma gondii: an AIDS enhancing cofactor.

Disseminated toxoplasmosis, one of the most severe acquired immune deficiency syndrome (AIDS)-associated infections in humans, is believed to develop from a latent infection after the cellular immune system is suppressed by human immunodeficiency virus type 1 (HIV-1). However, Toxoplasma gondii may serve as a cofactor in enhancing the immunodeficiency induced by HIV-1. This hypothesis is supported by the facts that: 1) co-infection with other pathogens in humans infected with HIV-1 may enhance the progression of the disease to AIDS; and 2) concomitant infection with T. gondii enhances feline immunodeficiency virus-induced immune dysfunction and is likely to cause a more rapid disease onset than an infection with HIV alone. It is possible that T. gondii infection induces tumor necrosis factor (TNF) production. TNF then stimulates the induction of T-cell proteins that bind to the long terminal repeat of HIV-1. This binding at the repeat site then leads to increased HIV-1 activation which causes the dysfunction of CD4 cells and a resulting immunodeficiency that allows even greater amounts of T. gondii replication.

AIDS-Related Opportunistic Infections↗

Immunological changes in cats with concurrent Toxoplasma gondii and feline immunodeficiency virus infections.

To examine the immunological changes in cats concurrently infected with feline immunodeficiency virus (FIV) and Toxoplasma gondii, kittens (four per group) were inoculated with FIV, T. gondii, both agents, or no pathogens. Blood mononuclear cells and plasma were collected weekly for lymphocyte assays and serology. At week 14, spleen and lymph node cells were used for lymphocyte assays; brains and mesenteric lymph nodes were used for isolation of T. gondii. More T. gondii organisms were present in tissues of the dually infected cats than in tissues of cats with toxoplasmosis alone. Two dually infected cats and one cat infected with T. gondii developed chorioretinitis. Spleen, lymph node, and blood mononuclear cells from dually infected cats had the greatest reduction in mitogenic responses. By week 3, cats infected with FIV underwent a decrease in the number of CD4 cells that was not changed by concurrent T. gondii infection; the number of CD8 cells increased only in cats infected with T. gondii alone. For cats infected with T. gondii, the responses of lymphocytes to T. gondii antigen were not affected by FIV infection; the responses to FIV antigen were negligible in all groups. Overall, this study indicates that FIV infection favors T. gondii proliferation. Also, the establishment of toxoplasmosis may enhance FIV-induced immunodeficiency and is likely to cause a more rapid disease progression than that from infection with FIV alone.

Animals↗

High levels of the (n-6) fatty acid 4,7,10,13,16-docosapentaenoate in the retinas of rabbits are reduced by feeding dietary fish oil from birth to adult life.

High levels of 4,7,10,13,16-docosapentaenoic acid [22:5(n-6)], a fatty acid usually associated with (n-3) fatty acid deficiency, have been reported in the retina of young rabbits. We studied the fatty acid composition of the rabbit retina throughout development, from birth to adult life. We also attempted to modify the fatty acid composition of the retina by the feeding of fish oil, high in docosahexaenoic acid [22:6(n-3), DHA]. Female rabbits were fed either a control or 2% fish oil diet through pregnancy and the nursing period. Weaned rabbits received the mothers' diet. In the retinas of control rabbits, 22:5(n-6) represented 3.7% of total fatty acids at birth, reached 15.1% at 9 wk and declined to 5.6% in adult rabbits. However, 22:6(n-3) increased steadily from birth onwards, from 3.8% of total fatty acids at birth to 19.6% in adults. Dietary fish oil increased the trace concentrations of long-chain (n-3) fatty acids in the milk to 10% of total fatty acids, reduced retinal 22:5(n-6) to less than or equal to 0.5% at all ages, and increased DHA to approximately 30% by 9 wk. Retinal phosphatidylethanolamine was even more sensitive to the impact of the fish oil diet, with DHA levels in newborn rabbits rising from 10% (control diet) to 43% of total fatty acids. These results demonstrated that 22:5(n-6) in the normal rabbit retina remains elevated (compared with other species) at all ages even as retinal DHA increases. The great increase of DHA in newborns whose mothers were fed fish oil suggests placental transfer of DHA and incorporation into retinal lipids.

Animals↗