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Biomedical subjects

R L Hopfer

Publications and source records attributed to R L Hopfer.

At least 37 records · Page 2Linked to original sources
PubMed1988

Structural studies on the carbohydrate moieties of human liver alpha-L-fucosidase.

alpha-L-Fucosidase was purified from human liver to apparent homogeneity and subjected to exhaustive digestion with Pronase. The resulting glycopeptides were isolated by gel filtration on Sephadex G-50 and further fractionated by Bio-Gel P-4 chromatography. Five glycopeptide fractions were obtained. The structures of the carbohydrate portions of all glycopeptide components were fully characterized by a combination of 500-MHz 1H NMR spectroscopy and carbohydrate composition analysis. Fraction I contained disialyl diantennary glycopeptides of the N-acetyllactosamine type. Fractions II and III contained predominantly mono(sialyl-N-acetyllactosaminyl) diantennary glycopeptides with the NeuAc alpha(2----6)Gal beta(1----4)GlcNAc beta(1----2) branch attached to alpha(1----3)-linked Man in II and to alpha(1----6)-linked Man in III. The N-acetyllactosamine-type glycopeptides in fractions I to III have a small portion (10-15%) of their Asn-linked GlcNAc residues substituted by additional alpha(1----6)-linked Fuc. Also, a minor portion of the NeuAc residues appeared to be attached to Gal in alpha(2----3) rather than alpha(2----6) linkage. Fraction IV contained a mixture of larger-size oligomannoside-type glycopeptides with a variable number (6 to 9) of Man residues. Smaller-size oligomannoside-type glycopeptides were found in fraction V, containing 3 or 5 Man residues; a small portion (10%) of the Man3GlcNAc2Asn component appeared to contain in addition a Fuc residue in alpha(1----6) linkage to the Asn-bound GlcNAc. The overall ratio of oligomannoside-type to N-acetyllactosamine-type carbohydrate structures was found to be 5:4. This article is the first account of the complete characterization of the oligomannoside-type structures in alpha-L-fucosidase; furthermore, the occurrence in alpha-L-fucosidase of mono(sialyl-N-acetyllactosaminyl) structures, Fuc-containing oligosaccharides, and NeuAc alpha(2----3) linked to Gal are reported for the first time.

Carbohydrate Sequence↗
PubMed1987

Mycobacterium fortuitum bacteremia in patients with cancer and long-term venous catheters.

Primary bacteremia due to Mycobacterium fortuitum is an uncommon occurrence. Four cases of M. fortuitum bacteremia in patients with cancer, one of whom was neutropenic, are presented. None of the patients had evidence of disseminated disease or endocarditis, and there was no mortality directly associated with this infection. Two patients had polymicrobial sepsis with skin commensal organisms. The infection was related to the use of long-term central venous catheters or recent instrumentation in all patients. M. fortuitum should be added to the growing list of organisms causing catheter-related infections.

Catheters, Indwelling↗
PubMed1987

Formulation, toxicity, and antifungal activity in vitro of liposome-encapsulated nystatin as therapeutic agent for systemic candidiasis.

Multilamellar vesicles containing nystatin (NYS) were compared with vesicles containing the free drug for toxicity to erythrocytes and for antifungal activity in vitro. Liposomal nystatin was as active as free NYS was against a wide variety of yeasts and fungi. The antifungal activity against Candida albicans was maintained with different liposome compositions and without sterols. Liposome encapsulation also protected the erythrocytes from the toxicity of free NYS.

Candida↗
PubMed1987

Toxicity and therapeutic effects in mice of liposome-encapsulated nystatin for systemic fungal infections.

The therapeutic activity of nystatin (NYS) incorporated in multilamellar liposomes (L-NYS) was studied in vivo. Hale-Stoner mice injected intravenously with various doses of L-NYS and free NYS showed a significant reduction in toxicity of NYS after the NYS was incorporated into liposomes (maximal tolerated doses, 16 and 4 mg/kg of body weight, respectively). The maximal tolerated dose of free NYS had no effect in the treatment of mice infected with Candida albicans, whereas L-NYS at an equivalent dose improved the survival of mice. A marked increase in survival was observed when L-NYS was administered in higher and multiple doses (total doses up to 80 mg/kg). Liposome encapsulation thus provided a means for intravenous administration of NYS, reducing its toxicity and making it an active systemic antifungal agent.

Animals↗
PubMed1987

Synergistic antifungal activity and reduced toxicity of liposomal amphotericin B combined with gramicidin S or NF.

Amphotericin B (AmpB) disrupts membrane integrity by binding to sterols in fungal and mammalian cell membranes. The gramicidins, which form pores in all membranes but exhibit poor antifungal activity, are too toxic to mammalian cells to be used systemically. This study demonstrated synergistic antifungal activity of free and liposomal forms of AmpB when combined with the free and liposomal forms of gramicidin S and gramicidin NF against five Candida strains. In vitro erythrocyte lysis was prevented by using the liposomal forms of all drugs tested alone or in combination. Presumably, AmpB increases accessibility of the fungal cell membrane to the gramicidins, while liposome encapsulation decreases the rate of transfer of the drugs to the mammalian cell membrane. Liposome encapsulation of inactive or toxic drugs, used in combination with liposomal AmpB, may give new life to drugs previously believed to be inactive or too toxic for therapeutic consideration.

Amphotericin B↗
PubMed1986

Serologic studies in hairy cell leukemia: high prevalence of Epstein-Barr and cytomegalovirus antibodies and absence of human T-cell lymphotrophic viruses antibodies.

Serum from 60 patients with hairy cell leukemia (HCL) were studied for the presence and the titers of antibodies to Epstein-Barr virus (EBV), cytomegalovirus (CMV) and human T-cell lymphotrophic viruses (HTLV). Eighty-three percent of the patients were seropositive for EBV, with a (reciprocal) geometric mean titer (GMT) of 960. Seventy-eight percent of the patients had antibodies to CMV with a GMT of 435. All 21 patients tested for HTLV I and HTLV III were seronegative; only one patient showed detectable antibodies to HTLV II. The potential role of these infections in the physiopathology of HCL is discussed.

Antibodies, Viral↗
PubMed1986

Semiquantitative cultures of intravascular catheters from cancer patients.

Three-hundred seventy-nine catheter tips were prospectively cultured by both a semiquantitative method and by broth culture, over a 2-month period. One hundred eleven of the catheters were culture-positive in broth, and 47 of these were also culture-positive by the semiquantitative method. Clinical signs of infection were reviewed for the 111 culture-positive catheters and for 50 of the 268 culture-negative catheters. Both culture-positive and culture-negative catheters were infrequently associated with local signs of infection (10% and 12%, respectively). Culture-positive catheters, however, were more likely to be associated with systemic signs of infection than were culture-negative catheters (15% and 2%, respectively). Among the culture-positive catheters, those that yielded greater than or equal to 15 colonies on semiquantitative culture were more likely to be associated with septicemias than were those with less than 15 colonies (22% and 6%, respectively). Nevertheless, there were five catheter-related bacteremias that were associated with catheters which were culture-negative on semiquantitative culture but culture-positive in broth. The proportion of patients with culture-positive and culture-negative catheters who were febrile was similar (30% and 42%, respectively). Semiquantitative cultures of catheters from cancer patients are useful, but the result should be interpreted with some caution.

Bacterial Infections↗
PubMed1986

Prophylaxis of Candida albicans infection with tuftsin.

The efficacy of tuftsin, a naturally-occurring immunomodulating peptide, in the prophylaxis of disseminated Candida albicans infections in mice was studied. The intravenous administration of tuftsin caused prolonged survival at all concentrations tested.

Animals↗
PubMed1985

Solubilization and characterization of pellet-associated human brain alpha-L-fucosidase activity.

The pellet-associated portion of human brain alpha-L-fucosidase (which represents approx. 20% of the homogenate activity) was solubilized with 0.5% (w/v) Triton X-100, characterized with regard to several properties and compared with the corresponding properties of the soluble supernatant-fluid enzyme in an attempt to find a second alpha-L-fucosidase in human brain. The solubilized and soluble alpha-L-fucosidase activities exhibited complete stability after storage at 2-4 degrees C for up to 29 days, comparable thermostability after preincubation at 50 degrees C, comparable apparent Km values (0.07-0.08 mM) for 4-methylumbelliferyl alpha-L-fucopyranoside, comparable hydrophobicity, comparable isoelectric-focusing profiles (six major forms, with pI values between 4.5 and 5.8) and comparable immunoprecipitation curves (with the IgG fraction of antisera prepared against human liver alpha-L-fucosidase). Differences in three properties were found between solubilized and soluble alpha-L-fucosidase activities: the solubilized activity was less stable to storage at -20 degrees C, had a 0.5-pH-unit neutral shift in its pH optimum (6.0) and had smaller Mr forms after gel filtration on Sephadex G-200. The overall results indicate that the pellet-associated and soluble portions of human brain alpha-L-fucosidase are quite similar in most of their properties. Thus there is still no compelling evidence for the existence of a second mammalian alpha-L-fucosidase.

Brain↗
PubMed1985

Prophylaxis of murine candidiasis via application of liposome-encapsulated amphotericin B and a muramyl dipeptide analog, alone and in combination.

The present study was conducted to examine the effect of a lipophilic analog of muramyl dipeptide, 6-O-stearoyl-N-acetylmuramyl-L-alpha-aminobutyryl-D-isoglutamine (6-O-S-Abu-MDP), a macrophage activator, on the prophylactic activity of liposomal amphotericin B (L-AmpB) against disseminated candidiasis in mice. Multilamellar vesicles containing AmpB and (6-O-S-Abu)-MDP were prepared by using dimyristoyl phosphatidylcholine and dimyristoyl phosphatidylglycerol (7:3 molar ratio). Hale-Stoner mice (6 to 8 weeks old) were injected with 7 X 10(5) CFU of Candida albicans 336 isolated from a patient. Groups of mice were injected intravenously with different doses of L-AmpB and L-(6-O-S-Abu)-MDP, individually or in combination, 2 days before challenge with C. albicans. The mice were injected with a fixed dose of L-AmpB (1.2 mg/kg in 400 mg of lipid per kg) and various doses of L-(6-O-S-Abu)-MDP (0.6, 1.2, 2, and 4 mg/kg in 400 mg of lipid per kg) or vice versa. Other control groups included untreated mice and those receiving empty liposomes (400 mg of lipid per kg), free AmpB (0.6 mg/kg), or free (6-O-S-Abu)-MDP (4 mg/kg). The mice receiving L-AmpB (1.2 mg/kg) plus L-(6-O-S-Abu)-MDP (0.6 to 4.0 mg/kg) survived up to 25 to 30 days as compared with those injected with L-AmpB alone (15 days) or with L-(6-O-S-Abu)-MDP alone (10 to 15 days). All the mice in other control groups died within 7 to 11 days. The kidney cultures of the mice that received L-AmpB (4 mg/kg) plus L-(6-O-S-Abu)-MDP (1.2 mg/kg) were free of C. albicans infection, unlike those injected with L-AmpB. Variance analysis of these findings indicates a synergistic activity between L-AmpB and L-(6-O-S-Abu)-MDP in the prophylaxis of candidiasis.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1985

Enzyme release of antigen from Streptococcus faecalis and Listeria monocytogenes cross-reactive with Lancefield group G typing reagents.

Enzyme extraction methods are commonly used to release antigen for Lancefield serogrouping of streptococci. Recently, up to 47% of enterococci have been found to possess antigens cross-reactive with both the group D and the group G grouping reagents. We investigated whether the organisms had recently emerged or whether changes in extraction methods (enzyme extraction) have resulted in our awareness of their existence. We found that approximately 20% of our enterococcal isolates released material cross-reactive with the group G reagents. These organisms have been present for at least 6 years, and probably for many more. In addition, we found that most strains of Listeria monocytogenes also released antigen cross-reactive with the group G reagent. The clinical significance of these findings is also discussed.

Antigens, Bacterial↗
PubMed1985

Serum neutral alpha-D-glucosidase from patients with cystic fibrosis and chronic pulmonary disease.

Previous studies have indicated that alpha-D-glucosidase activity is increased and exhibits abnormal properties in tissues from patients with cystic fibrosis (CF). In the present investigation serum alpha-D-glucosidase from patients with CF and from patients with chronic pulmonary disease (e.g. asthma and bronchiectasis) has been studied to determine the specificity of the alpha-D-glucosidase alteration(s) in CF sera. Both groups of patients have elevated alpha-D-glucosidase activity levels and similarly abnormal isoelectric focusing profiles with significantly less activity associated with acidic enzymatic forms (i.e. having isoelectric points below 4.8). These results suggest that the abnormalities of CF serum alpha-D-glucosidase may be secondary to chronic pulmonary disease and emphasize the importance of including appropriate pathological controls in biochemical studies on CF.

Adolescent↗
PubMed1985

Effects of tuftsin on postsplenectomy sepsis.

Tuftsin is a tetrapeptide within the CH2 domain of the IgG immunoglobulin. Enzymatically cleaved from its parent globulin, it increases the phagocytic activity of macrophages, monocytes, and neutrophils by specific receptor mechanisms. In splenectomized hosts the circulating levels of tuftsin are reduced. Postsplenectomy sepsis is due to impaired clearance of intravascular bacteria; it has been postulated that tuftsin deficiency may contribute to this impairment. In this experiment splenectomized DBA/2 mice were subjected to pneumococcal sepsis. The groups of mice treated with tuftsin and those that received autotransplanted splenic tissue had significantly improved survival rates. We conclude that tuftsin deficiency plays a role in postsplenectomy sepsis and that treatment with synthetic tuftsin protects the splenectomized host against pneumococcal septic death.

Animals↗
PubMed1984

Liposome-encapsulated amphotericin B for treatment of disseminated candidiasis in neutropenic mice.

The relative efficacies of free amphotericin B (Amp B) and liposome-encapsulated Amp B (L-AmpB) in the treatment of established Candida albicans infection in mice rendered neutropenic with cyclophosphamide were studied. AmpB was entrapped in multilamellar liposomes composed of dimyristoyl phosphatidylcholine and dimyristoyl phosphatidylglycerol in a molar ratio of 7:3. Infected mice treated with single doses of 3 mg L-AmpB/kg of body weight had an increased survival time compared with those injected with either single (dose, 0.8 mg/kg) or multiple doses (dose, 0.8 mg/kg daily for five days) of free AmpB. When treatment was delayed beyond three days postinfection, neither single nor multiple doses of free AmpB resulted in increased survival, whereas treatment with single-dose L-AmpB (dose, 4 mg/kg) showed efficacy when delayed as much as four days postinfection. Five days postinfection only higher doses (dose, 5.6 mg-11.2 mg/kg) of L-AmpB improved survival time and the renal impairment present in the infected animals. These data provided a rational basis for using high-dose L-AmpB to treat fungal diseases in humans, particularly in neutropenic patients.

Agranulocytosis↗