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Biomedical subjects

M S Wolfe

Publications and source records attributed to M S Wolfe.

At least 19 recordsLinked to original sources

4'-modified analogues of aristeromycin and neplanocin A: synthesis and inhibitory activity toward S-adenosyl-L-homocysteine hydrolase.

The carbocyclic adenosine analogues aristeromycin and neplanocin A both display significant S-adenosyl-L-homocysteine (AdoHcy) hydrolase inhibitory activity and broad-spectrum antiviral effects. Since phosphorylation of the 4'-hydroxymethyl substituent has been implicated with the cytotoxicity of these compounds, various analogues modified at this position were synthesized utilizing a key cyclopentenone intermediate 3 which can be derived from several members of the natural chiral pool. Cyclopentenone 3 underwent a highly stereoselective conjugate addition with organocuprate reagents, and the 1,4-adducts so formed were then readily elaborated to the corresponding 4'-modified aristeromycin analogues. Alternatively, quenching the enolate intermediate of the organocuprate conjugate addition with methanesulfinyl chloride followed by pyrolytic syn elimination resulted in the formation of 4'-modified neplanocin A intermediates. Three of the final compounds (1b, 1c, and 1e) displayed inhibitory activity toward AdoHcy hydrolase in the nanomolar range.

Adenosine

High affinity binding proteins for pancreatic polypeptide on rat liver membranes.

We report here the identification on rat liver plasma membranes and microsomes of proteins that bind pancreatic polypeptide (PP) with high affinity and specificity (plasma membranes: KD = 4.6 nM, Bmax = 3.28 pmol/mg protein; microsomes: KD = 3.45 nM, Bmax = 18.7 pmol/mg protein). These binding proteins appeared coupled to a G-protein, since 0.1 mM guanosine 5'-O-(3-thiotriphosphate) decreased the affinity by half. When 125I-labeled PP-binding protein complexes covalently cross-linked with disuccinimido suberate were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, two radioactive bands with M(r) values of 52,000 and 38,000 were demonstrated. Both bands were inhibited by unlabeled PP with an IC50 of approximately 5 nM (but not by neuropeptide Y or peptide YY). After the cross-linked complexes were solubilized from liver microsomes with 0.2% Triton X-100 and gel-filtered, they did not interact with the lectins wheat germ agglutinin, Ulex europaeus agglutinin, Ricinus communis agglutinin, and soy bean agglutinin. That these binding proteins may not be glycosylated was further supported by the failure of either peptide N-glycosidase F and endo-beta-N-acetylglucosaminidase F to alter the size of the PP-binding protein complexes on gel electrophoresis. These PP-binding proteins may serve as receptors and mediate a hepatic effect of PP.

Animals

Tropical diseases in immigrants and internationally adopted children.

Immigrants, particularly those from the developing world, make up a significant number of tropical disease cases seen in a temperate climate. Internationally adopted children are another group in which tropical and other infectious diseases must be considered. The differential diagnoses of various syndromes in these populations in relation to relatively more common tropical diseases are reviewed.

Adoption

Age- and dietary fat-related effects on biliary lipids and cholesterol gallstone formation in African green monkeys.

The effects of age and dietary fat on bile cholesterol saturation index (CSI) and cholesterol gallstone formation were studied in three age groups of male African green monkeys. Animals were fed semipurified diets containing cholesterol (0.34 g/100 g diet) and 42% of energy as saturated or polyunsaturated fat. Animals were killed at 16 (pre-pubertal), 32 (peri-pubertal) or 60 (young adult) mo of age; the presence of gallstones was determined and gallbladder bile was analyzed for CSI and bile acid composition. Cholesterol gallstones were present in 9% of 60-mo-old animals, compared with a 42% incidence in adult animals fed these same diets for 5 y. Gallbladder bile from the 32-mo-old group contained significantly more cholesterol and had a higher CSI as compared with the other age groups. Dietary fat had no effect on biliary lipid composition. We conclude that the increase in CSI around the time of puberty in male monkeys is not clinically significant in terms of gallstone formation, and that polyunsaturated fat feeding is not associated with adverse effects. Because the incidence of gallstone formation in these young adults was lower than that seen in older adults, a minimal amount of time consuming a lithogenic diet as an adult seems to be required for stone genesis.

Aging

Giardiasis.

Giardiasis is one of the most common pathogenic intestinal protozoal infections worldwide. Giardia lamblia is the most frequently identified etiologic agent in outbreaks associated with the ingestion of surface water, often due to ineffective filtration or pretreatment. In addition to humans, other sources of infection include beavers, perhaps muskrats, and possibly domestic animals. A low infecting dose (10 to 25 cysts) is reported to be sufficient to produce human infection. Clinical manifestations range from asymptomatic to a transient or persistent acute stage, with steatorrhea, intermittent diarrhea, and weight loss, or to a subacute or chronic stage that can mimic gallbladder or peptic ulcer disease. Diagnosis is usually based on repeated stool examinations but examination of duodenal fluid or biopsy material may also be necessary. Enzyme immunoassay or indirect immunofluorescence methods for direct detection of antigen or whole organisms in clinical specimens have also been developed. These tests are reported to be more sensitive than routine stool examination. Demonstration of serum immunoglobulin M and G antibodies may help differentiate recent from past infection or help detect recurrence in individuals who have been treated previously. Serum immunoglobulin A levels may be a useful indicator of exposure in waterborne outbreaks of diarrhea. Drugs available for treatment within the United States include metronidazole, quinacrine hydrochloride, and furazolidone.

Animals

Eosinophilia in the returning traveler.

Eosinophilia in a traveler returning from the developing world should first and foremost suggest the possible presence of a helminth parasite. Protozoal parasites are much less commonly associated with eosinophilia. Other entities to be considered include allergies, drug reactions, and numerous other miscellaneous causes.

Eosinophilia

Travel medicine and travel clinics.

In response to the vast number of American travelers to the developing world, the discipline of Travel Medicine has become an emerging specialty. There are presently no formal Board or other requirements to practice Travel Medicine, but bona fide practitioners of this field, who also usually direct travel clinics, should at the least be well-trained and experienced in tropical medicine and medical aspects of travel, and have had considerable overseas work experience. The concept of travel medicine and the need for travel clinics operated by well-qualified physicians are discussed. The areas of involvement of travel clinics in protecting the health of the traveler are described.

Ambulatory Care Facilities

Acute diarrhea associated with travel.

Travelers' diarrhea, an acute illness that affects between 20 and 50 percent of travelers to high-risk areas, is usually acquired by eating contaminated food, drinking contaminated water, or coming in contact with the contaminated hands of an infected person. Travelers' diarrhea can be caused by bacterial, viral, and parasitic agents. The Travelers' Diarrhea Consensus Conference has recommended prophylactic measures, which include proper preparation of food and beverages, nonantimicrobial agents, and antimicrobial agents. The newer quinolone antibiotics and bismuth subsalicylate may also be useful prophylactically. Appropriate treatment methods include oral fluids and electrolyte replacement, nonspecific agents such as bismuth subsalicylate, antimotility agents such as loperamide hydrochloride and diphenoxylate hydrochloride, and antimicrobial and antiparasitic agents.

Acute Disease

Vaccines for foreign travel.

Exotic infections are a significant threat to the child traveling to or going to live in the developing world. Vaccines are available that can prevent some of these infections. It is essential that basic routine childhood vaccination be up to date and that necessary modifications be made from the usual schedule in the United States. The current requirements and local disease conditions (both endemic and epidemic) for each country to be visited must be known so that appropriate vaccines are received. Resources for this information are listed. Details for each vaccine are given, including indications, dose, booster, side effects, contraindications, and other specific information.

Breast Feeding

Giardiasis.

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Body Fluids

Giardiasis.

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Acute Disease