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Biomedical subjects

J Fink

Publications and source records attributed to J Fink.

At least 19 recordsLinked to original sources
PubMed1989

The chemical synthesis of cecropin D and an analog with enhanced antibacterial activity.

Cecropin D was synthesized by solid-phase methods and shown to be homogeneous and of correct composition and molecular weight. It was indistinguishable from natural cecropin D and constitutes a structure proof for this peptide. Several analogs of cecropin D were synthesized and used to draw conclusions about the structural features contributing to antibacterial activity. They included [Lys1]cecropin D, [Gln3, Leu4] cecropin D, and cecropin D-(9-37). It was concluded that a strongly basic NH2-terminal segment is a prerequisite for antibacterial activity. A hybrid analog cecropin A-(1-11) D-(12-37) was designed and predicted to have enhanced potency. It was found to be 5 to 55 times as active as cecropin D against six of the bacteria tested and was slightly more active than cecropin A. However, against Bacillus subtilis Bs11 the analog was 6 times more active than cecropin A.

Amino Acid Sequence↗
PubMed1989

Design, synthesis and antibacterial activity of cecropin-like model peptides.

In order to investigate structure-activity relationships of cecropins, model peptides that mimic certain structural features of the cecropin molecules were designed and synthesized. The conformational analysis of cecropins and the design of the model peptides were based on Chou-Fasman calculations. The peptides were synthesized by solid-phase methods and purified by reverse-phase liquid-chromatography on C18-silica columns. Their secondary structures were studied by circular dichroism measurements. Antibacterial activities against seven test organisms were determined and compared to the activities of the natural cecropins A and B. These results were discussed on the basis of structural features of the model peptides and on model mechanisms. It was concluded that high antibacterial activity for this class of compounds requires a basic helical amphipathic N-terminal segment that is connected to a hydrophobic helical C-terminal segment by a flexible non-helical hinge region.

Amino Acid Sequence↗
PubMed1988

Channel-forming properties of cecropins and related model compounds incorporated into planar lipid membranes.

Cecropins, positively charged antibacterial peptides found in the cecropia moth, and synthetic peptide analogs form large time-variant and voltage-dependent ion channels in planar lipid membranes in the physiological range of concentration. Single-channel conductances of up to 2.5 nS (in 0.1 M NaCl) were observed, which suggests a channel diameter of 4 nm. Channels formed by the peptides cecropin AD and MP3 had a permeability ratio of Cl-/Na+ = 2:1 in 0.1 M NaCl. A comparative study of the three cecropins, cecropins A, B, and D, and of six synthetic analogs allowed determination of structural requirements for pore formation. Shorter amphipathic peptides did not form channels, although they adsorbed to the bilayer. A flexible segment between the N-terminal amphipathic region and the C-terminal more hydrophobic region of the peptide was required for the observation of a time-variant, voltage-dependent conductance. Cecropin AD was the most effective voltage-dependent pore-forming peptide and was also the most potent antibacterial peptide against several test organisms. A positive surface charge or cholesterol in the bilayer reduced the conductances caused by cecropin AD or MP3 by at least 5-fold. This behavior is consistent with the known insensitivity of eukaryotic cells to cecropins. Our observations suggest that the broad antibacterial activity of cecropins is due to formation of large pores in bacterial cell membranes.

Amino Acid Sequence↗
PubMed1987

Niemann-pick variant disorders: comparison of errors of cellular cholesterol homeostasis in group D and group C fibroblasts.

Fluorescence microscopic examination of filipin-stained cultured skin fibroblasts derived from two brothers with group D Niemann-Pick disease revealed abnormal storage of low density lipoprotein (LDL)-derived cholesterol. LDL stimulation of intracellular cholesteryl ester synthesis was severely compromised in the Niemann-Pick D fibroblasts, as it also was in fibroblasts obtained from Niemann-Pick C patients. Cholesteryl ester synthesis was intermediately deficient in cells derived from an obligate group-D heterozygous carrier. Activity of acyl-CoA:cholesterol acyltransferase was within the normal range in cell-free extracts of both LDL-depleted and LDL-supplemented cultures of Niemann-Pick C and D fibroblasts. Incubation of Niemann-Pick D fibroblasts with LDL did not lead to as high a level of intracellular cholesterol accumulation as the excessive storage observed with Niemann-Pick C fibroblasts. These findings suggest that the Niemann-Pick variant disorders may represent a family of specific and possibly individual mutations that disrupt cellular cholesterol homeostasis.

Adult↗
PubMed1987

Operative technique and results of subtotal splenectomy for Gaucher disease.

Patients with type 1 (adult form) Gaucher disease complicated by massive splenomegaly and hypersplenism have previously been treated by total splenectomy. Subtotal splenectomy in Gaucher disease will retain splenic tissue which may protect the patient from the risk of overwhelming sepsis. Removal of at least 85 per cent of the splenic mass is necessary to eliminate hypersplenism and to decrease splenic size. The surgical technique and outcome of four patients undergoing subtotal splenectomy for massive splenomegaly due to type 1 Gaucher disease are discussed.

Adult↗
PubMed1986

Gaucher disease: sonographic appearance of the spleen.

Ultrasonographic (US) examinations of the upper abdomen were performed in 80 patients with Gaucher disease. Of the 49 patients that had not undergone splenectomy, 47 had splenic enlargement. Sixteen patients had multiple lesions in the spleen. Most patients had discrete hypoechoic lesions that corresponded pathologically to focal homogeneous clusters of Gaucher cells. Several patients had similar lesions that were hyperechoic and were composed of Gaucher cells and fibrosis or infarction. A few patients had a geographic pattern of irregular areas of involvement of Gaucher cells among normal splenic parenchyma. The liver was often enlarged but otherwise sonographically unremarkable. Patients with Gaucher disease often have US examinations of the left upper quadrant for abdominal pain. A variety of US findings in the spleen typical for Gaucher disease should be recognized and not interpreted as acute changes.

Adolescent↗
PubMed1986

A new method for reporting the sources of abnormal activities of lactate dehydrogenase in serum.

We have developed and tested a new method to increase the diagnostic usefulness of measurements of lactate dehydrogenase (LDH; EC 1.1.1.27) isoenzymes. The method estimates the separate contributions from enzymatically distinct organ clusters (e.g., heart/kidney/erythrocyte, liver/muscle, lung) to the total activity of LDH in serum. To test this method, we monitored serum LDH isoenzymes over the entire hospital course of 73 patients admitted to the intensive-care unit with chest pain, myocardial infarction, or serious hemodynamic disturbances. The organ-specific estimates provided useful information beyond measurements of the original isoenzymes. The sensitivity and specificity of this new method in detecting acute myocardial infarction, as well as concomitant disorders involving the liver or lung, are significantly greater than those of other diagnostic indices or pathologists' judgments. Serial plots of the organ-specific estimates may provide additional insight into evolving pathophysiological processes.

Aged↗
PubMed1985

Effects of hypothyroidism on the DNA, carbohydrate, soluble protein and sialic acid contents of rat submandibular glands.

Submandibular glands are a target organ of thyroid hormones. This study examined the effects of hypothyroidism on the biochemical characteristics of these glands in the rat. There were no effects on the neutral sugar and DNA contents. However, soluble protein concentrations (micrograms/mg wet weight) were significantly decreased and sialic acid concentrations micrograms/mg soluble protein) were significantly elevated.

Animals↗
PubMed1979

A study of HLA-A, B, C, and DR specificities in pigeon breeder's disease.

The frequencies of HLA-A, -B, and -C antigens were determined among 51 symptomatic pigeon breeders, 102 asymptomatic pigeon breeders, and 100 normal blood donors. The HLA-DR specificities were also studied in 32 symptomatic and 29 asymptomatic pigeon breeders. All subjects were white. Symptomatic subjects were defined by the development of respiratory symptoms or decreased pulmonary function after aerosol challenge with pigeon serum. Asymptomatic subjects were comparably exposed to pigeons but had no pulmonary signs or symptoms after aerosol challenge. No significant association was found between any of the tested HLA specificities and pigeon breeders. This lack of association and the observed paucity of multiplex families indicate that HLA complex genetic factors tested in this study do not favor the development of pigeon breeder's disease in exposed persons.

Alveolitis, Extrinsic Allergic↗