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Biomedical subjects

K Bloch

Publications and source records attributed to K Bloch.

At least 19 recordsLinked to original sources
PubMed1992

Sterol molecule: structure, biosynthesis, and function.

This review briefly summarizes key researches on the structure of the sterol molecule from its very beginnings to the definitive elucidation in 1932. Cholesterol biosynthesis treated in somewhat greater detail covers the period from the 1930s to the 1960s. As a historic contribution, it presents researches previously published in numerous books, reviews, and original papers. The selection of topics, dictated by limits of time and space, is necessarily arbitrary and a personal choice. Readers of this journal will be familiar with the relevant chemical structures. Structural formulas are therefore omitted.

Cholesterol↗
PubMed1990

[Pneumocystis carinii pneumonia in HIV infection: better prognosis because of early diagnosis].

The clinical presentation of 60 consecutive Pneumocystis carinii pneumonias in 58 HIV-infected patients (48 men, 10 women, mean age 34 [22-53] years) was prospectively evaluated from April to August 1989 and compared with 60 consecutive P. carinii pneumonias in 59 HIV-infected patients (55 men, 4 women, mean age 37.5 [22-60] years) between 1981-88. Mortality rates within 14 days after diagnosis of P. carinii pneumonia were 50% (8 of 16 patients) until 1985, 20.5% (9 of 44) between 1986 and August 1988, and 1.7% (one of 60) in 1989. The degree of severity of the pneumonias at time of diagnosis was markedly lower in 1989, as shown by following parameters (averages of 1989, compared with averages of 1981-88): lactate dehydrogenase 540 (250-1419) U/l versus 680 (235-1920) U/l (not significant); alveolo-arterial difference of partial oxygen tension (pA-aO2) 22.9 (0.5-73.5) mmHg versus 39.7 (19-70) mmHg (P less than 0.001); score of radiological findings 1.4 (0-3) versus 2.7 (0-4) (P less than 0.001). In 1989, mainly clinical symptoms (dry cough: 57 of 60 cases, dyspnea: 44 of 60 cases, fever: 43 of 60 cases) initiated the diagnostic procedure: chest radiographs, lactate dehydrogenase and pA-aO2 were normal in 13, 25 and 33 episodes, respectively. The lower mortality rate of P. carinii pneumonia could not primarily be explained by therapeutical progress since the treatment of choice did not change fundamentally since 1981. Above all, early diagnosis fundamentally determined the probability of survival.

Adult↗
PubMed1990

[Experiences with long-term transtracheal oxygen therapy].

A transtracheal catheter (TTC) (Scoop) was implanted in 24 patients (19 men, 5 women) with a mean age of 64 +/- 9 (47 to 78) years. The pO2 was 6.78 +/- 1.65 kPa. Two patients suffered from pulmonary restriction, 22 from severe COPD with a FEV1 of 880 +/- 165 ml. Purulent tracheitis developed in six patients. The pre-Scoop catheter had to be removed in three. In four patients, bronchoscopic aspiration of mucus plugs adhering to the tip of the TTC was necessary. In one patient, the TTC was removed after an uneventful course due to patient's discomfort; another patient no longer qualified for LOT. 19 patients were using the TTC without major problems. Of those, five have died due to severe lung disease. By using TTC, oxygen consumption is halved for the same degree of oxygenation. 12 are using a demand valve device (Oxymatic), which allows a further conservation of oxygen. Patients prefer LOT by a TCC for cosmetic reasons and lack of nasal discomfort.

Aged↗
PubMed1990

[Obstructive sleep apnea syndrome in a child with trisomy 21].

Pulmonary hypertension without any cardiovascular malformation was diagnosed by heart catheterization in a 4 year old girl with trisomy 21. A suspected obstructive sleep apnea syndrome was confirmed by polysomnography which revealed numerous obstructive apneas and hypopneas (apnea-index 23/h) with marked oxygen desaturation and a disturbed sleep pattern. Three months after adenotonsillectomy the mother reported her daughter having a quiet sleep without snoring. Polysomnography did not show any apnea nor any oxygen desaturation below 90%. A decrease of the pulmonary artery pressure was documented. Facial dysmorphias and muscle hypotonia predispose patients with trisomy 21 to obstructive sleep apnea, especially if hypertrophy of tonsills and adenoids coexist. Frequent arousals and hypoxia during sleep can result in failure to thrive and pulmonary hypertension. These consequences can be prevented by early diagnosis and treatment.

Adenoidectomy↗
PubMed1990

Sterol effects on phospholipid biosynthesis in the yeast strain GL7.

Cells of the yeast sterol auxotroph GL7 were grown on either ergosterol or cholesterol to mid-logarithmic phase and total membrane fractions prepared. Activities of phospholipid biosynthetic enzymes in the two cell types were determined. The rates of phosphatidyl-ethanolamine-phosphatidyl-choline-N-methyl transferase and acyl-CoA-alpha-glycerol-3-phosphate transcylase were significantly greater in ergosterol-grown than in cholesterol-grown cells. These reactions were also inhibited by the polyene antibiotic filipin. By contrast the activities of long-chain fatty acyl-CoA synthetase, CTP-phosphatidate-cytidyl transferase, phosphatidylserine decarboxylase and of phosphatidylinositol synthetase were identical in the two (ergosterol and cholesterol) cultures and unaffected by filipin. The ergosterol effect on phosphatidyl-ethanolamine N-methyl transferase was greatest in cells harvested in early log phase, intermediate in the mid-log phase cells, and not significant in stationary phase cells.

Cholesterol↗
PubMed1989

[Right heart endocarditis].

Symptoms, cause and survival in 11 patients with right heart endocarditis hospitalized from 1973 to April 1989 were analyzed. The main symptoms were high fever, chest pain and dyspnea due to septic pulmonary emboli. The age of the 6 men and 5 women ranged from 19 to 66 years. 9 intravenous drug abusers and a patient with a pacemaker and carcinoma of the colon had tricuspid valve endocarditis. In another patient without known risk factors the aortic valve was affected as well. Staphylococcus aureus was isolated in 9 cases, in two as a double infection with Candida albicans and streptococcus group G respectively; beta-hemolytic streptococci group A and enterococci were found in the two remaining patients. Based on the well known high sensitivity of 2D-echocardiography, only cases with detectable tricuspid valve vegetations have been included in this retrospective study since this method became available. 10 patients were treated by antibiotics. In a single patient the tricuspid valve was removed after antibiotic pretreatment and an artificial valve was implanted 7 months later. Two patients died, one a few days after admission due to overwhelming sepsis, and one from intracerebral hemorrhage caused by an embolized aortic valve vegetation. The other patients have survived for a mean 44 months (range 2 to 183 months). Endocarditis of the right heart differs from left heart endocarditis through its typical clinical presentation, a different spectrum of microorganisms and a favourable outcome under antibiotic treatment.

Adult↗
PubMed1989

Preventing fraud.

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Biomedical Research↗
PubMed1989

6-Fluorocholesterol as a growth factor for the yeast mutant GL7.

6-Fluorocholesterol supports the growth of the sterol-requiring yeast mutant GL7 albeit less efficiently than cholesterol or ergosterol. When the fluoro analogue is combined with very much smaller amounts of cholesterol, the growth response to the sterol pair is synergistic, i.e., greater than additive. On further addition of trace amounts of ergosterol to the 6-fluorocholesterol-cholesterol pair, an additional synergistic growth response is observed. On 6-fluorocholesterol alone, the growth rate of the yeast mutant is slow initially, but after several transfers of such cells to the same media containing the fluoro analogue, growth improves substantially. When incorporated into artificial membranes, cholesterol and its 6-fluoro analogue have essentially identical effects on membrane fluidity as judged from microviscosity measurements. The contrasting responses of artificial membranes and whole cells to the 6-fluoro analogue of cholesterol might be due to sterol-protein interactions in natural membranes.

Cholesterol↗
PubMed1988

Phosphatidylcholine synthesis in yeast.

The two pathways for the biosynthesis of phosphatidylcholine, by way of phosphocholine and by methylation of phosphatidylethanolamine, in wild-type yeast (Saccharomyces cerevisiae) and in the yeast mutant GL7 have been compared. The mutant requires for growth a sterol, unsaturated fatty acids, and methionine. The uptake of labeled choline or labeled methionine and their conversion to phosphatidylcholine were determined in both cell types. The activities of the major enzymes for both pathways were assayed in vitro. We find that the methylation pathway is predominant in both wild-type and mutant cells though the overall activity of the choline pathway is lower in the yeast mutant. The methionine analogue ethionine inhibits the growth of the mutant more strongly than growth of wild-type yeast. Ethionine, while a powerful inhibitor of phosphatidylcholine synthesis by methylation, stimulates the choline pathway in both cell types.

Choline↗
PubMed1987

Summing up.

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Biochemistry↗
PubMed1985

Studies on the mode of action of sterol carrier protein in the dehydrogenation of 5-cholest-7-en-3 beta-ol.

Sterol carrier protein (SCP) (Ritter, M. C., and Dempsey, M.E. (1973) Proc. Natl. Acad. Sci. U.S.A. 70, 265-269) promotes the microsomal dehydrogenation of 5-cholest-7-en-3 beta-ol (lathosterol) to 7-dehydrocholesterol. This promotion occurs whether the substrate is exogenous or preincorporated into microsomes. Similarly, SCP promotes an intermembrane transfer of lathosterol from one microsomal population to another (Ishibashi, T., and Bloch, K. (1981) J. Biol. Chem. 256, 12962-12967). Here we present evidence for an SCP-mediated collisional interaction which results in the intermembrane transfer of sterol substrate and excludes a conventional substrate-carrier mechanism for SCP. Radioactive carboxymethyl SCP is shown to bind to microsomes and to anionic phospholipids but not to phosphatidylcholine. Treatment of microsomes with trypsin, but not with phospholipase A2, reduces SCP binding. Binding studies with small molecules substantiate the identity of SCP with Z-protein.

Animals↗
PubMed1985

Sterol control of the phosphatidylethanolamine-phosphatidylcholine conversion in the yeast mutant GL7.

The relatively slow growth rate of the yeast mutant GL7, a sterol auxotroph, on medium containing cholesterol is markedly accelerated by supplementation with small amounts of ergosterol. Under these conditions (sterol synergism) cellular phospholipid synthesis is enhanced. We now find that one of the ergosterol-stimulated processes is the methylation of phosphatidylethanolamine to phosphatidylcholine. This is shown by comparing methyltransferase activities of membrane preparations derived from cells grown on either ergosterol, cholesterol, or the synergistic sterol pair. Incorporation of 32P from [gamma-32P]ATP into the yeast membranes is rapid and greater when ergosterol-grown cells rather than cholesterol-grown cells are the source of membranes.

Adenosine Triphosphate↗
PubMed1985

Stimulation by unsaturated fatty acid of squalene uptake in rat liver microsomes.

Supernatant protein factor (SPF) and anionic phospholipids such as phosphatidylglycerol (PG) stimulate squalene epoxidase activity in rat liver microsomes by promoting [3H]squalene uptake as well as substrate translocation (Chin, J., and K. Bloch. 1984. J. Biol. Chem. 259: 11735-11738). This process is postulated to be membrane-mediated and not carrier-mediated. Here we show that treatment of PG with phospholipase A2 in the presence of bovine serum albumin abolishes the stimulatory effect of SPF on epoxidase activity. Disaturated fatty acyl-PGs are not as effective as egg yolk lecithin PG in the SPF effect. These findings suggest an important role for the unsaturated fatty acid moiety of PG. We also show that at submicellar concentrations, cis-unsaturated fatty acids stimulate microsomal epoxidase activity whereas saturated fatty acids do not. This effect is due to an increase in substrate uptake which in turn may facilitate substrate availability to the enzyme.

Animals↗
PubMed1979

Effects of a supernatant protein activator on microsomal squalene-2,3-oxide-lanosterol cyclase.

A soluble protein termed "supernatant protein factor" (SPF) that stimulates microsomal squalene epoxidase has been isolated in this laboratory (Ferguson, J.B., and Bloch, K. (1977) J. Biol. Chem. 252, 5381-5385). We now show that the purified protein also stimulates microsomal squalene-2,3-oxide leads to lanosterol cyclase but has no effect on the subsequent conversion of lanosterol to cholesterol. Phospholipid, specifically phosphatidylglycerol or phosphatidylethanolamine, is required for maximal stimulation of the cyclase by purified SPF. The response of microsomal squalene epoxide-lanosterol cyclase to SPF was abolished by pretreatment of the membranes with phospholipase A2 or by low concentrations of deoxycholate, indicating that an intact membrane system is required. Digestion of intact microsomes with trypsin had no effect on the SPF-stimulated cyclase activity. However, in the presence of 0.4% deoxycholate, trypsin completely inhibited microsomal squalene epoxide-lanosterol cyclase. We conclude that the cyclase is located on the luminal side of the microsomal membrane. SPF also significantly enhances the formation of lanosterol from squalene-2,3-oxide already bound to microsomes. This finding is constant with the proposal that SPF influences intramembrane events.

Animals↗