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Biomedical subjects

M Alexander

Publications and source records attributed to M Alexander.

At least 307 records · Page 17Linked to original sources

Phosphorus-containing pesticide breakdown products: quantitative utilization as phosphorus sources by bacteria.

Bacteria were isolated that could utilize representatives of the following ionic phosphorus-containing breakdown products of organophosphorus pesticides as sole phosphorus sources: dialkyl phosphates, dialkyl phosphorothioates, dialkyl phosphorodithioates, alkyl arylphosphonates, alkyl arylphosphonothioates, and alkyl alkylphosphonates. Utilization of each organophosphorus compound, which was complete for 7 of 12 compounds studied, was confirmed by determination of protein yield from the amount of phosphorus source consumed. This is the first report of the utilization of an ionic dialkyl thiophosphate or dithiophosphate by microorganisms.

Bacteria↗

Phosphonate utilization by bacteria.

Bacteria able to use at least one of 13 ionic alkylphosphonates of O-alkyl or O,O-dialkyl alkylphosphonates as phosphorus sources were isolated from sewage and soil. Four of these isolates used 2-aminoethylphosphonic acid (AEP) as a sole carbon, nitrogen, and phosphorus source. None of the other phosphonates served as a carbon source for the organisms. One isolate, identified as Pseudomonas putida, grew with AEP as its sole carbon, nitrogen, and phosphorus source and released nearly all of the organic phosphorus as orthophosphate and 72% of the AEP nitrogen as ammonium. This is the first demonstration of utilization of a phosphonoalkyl moiety as a sole carbon source. Cell-free extracts of P. putida contained an inducible enzyme system that required pyruvate and pyridoxal phosphate to release orthophosphate from AEP; acetaldehyde was tentatively identified as a second product. Phosphite inhibited the enzyme system.

Aminoethylphosphonic Acid↗

Specialized nutritional support and cancer.

Over a 7 1/2-year period, 94 cancer patients presenting considerable operative risk were managed by total parenteral nutrition (TPN). All were nutritionally depleted, had obstruction to the gastrointestinal tract or had postoperative complications such as enterocutaneous fistulas, evisceration or intra-abdominal sepsis, which left TPN as the only means of achieving anabolism. When TPN was started preoperatively and continued post-operatively (28 patients--Group 1), no deaths or significant complications occurred. When TPN was first started after life-threatening complications had occurred (58 patients--Group 2), the mortality was 17.2%, so that a high incidence of recovery was achieved. When TPN was used in inoperable cachectic patients (8 patients--Group 3) to enable them to tolerate radiotherapy or chemotherapy, the mortality was 37.5%. This latter group is small, but TPN is worthwhile in selected patients where significant palliation and improvement in the quality of life can occur. With careful technique, risk of sepsis with TPN was no greater than in noncancer patients.

Humans↗

[Hyperergic collagenoses. Clinical aspects, differential diagnosis and therapy (author's transl)].

On the basis of inpatient and outpatient observations of the longterm course in 44 patients with erythematodes disseminatus, 8 with periarteritis nodosa, 4 with Wegener's granulomatosis, 5 with dermatomyositis, 3 with giant cell arteritis and 9 with scleroderma the pathogenesis, differential diagnosis and therapy of these diseases is discussed. The differential diagnosis and longterm supervision being dealt with particularly thoroughly. Early recognition of the disease episodes and appropriate therapeutic action in the shape of increased doses of prednisolone are important. Additional cytostatics were given if the kidney was involved.

Adolescent↗

Liver toxicity after acetaminophen ingestion. Inadequacy of the dose estimate as an index of risk.

With increasing frequency, the physician is confronted with the problem of determining the risk of liver toxicity in a person who may have ingested an overdose of acetaminophen. To be effective, antidotal therapy must be given early after acetaminophen ingestion when the patient, despite the toxic injury occurring in his liver, may appear quite well. We have reviewed the cases of the first five persons who came to our institution with a history of having ingested a large overdose of acetaminophen. In each case plasma or serum acetaminophen levels were low and substantial liver injury did not occur. Measurement of acetaminophen levels, indicating the amount of drug absorbed, were a more reliable index of the risk of toxic liver injury and the need for antidotal therapy than the estimate of the dose ingested.

Acetaminophen↗

Further evidence for the regulation of bacterial populations in soil by protozoa.

After the addition to soil of large numbers of a cowpea Rhizobium strain, the population declined steadily until the numbers reached about 10(7)/g, and the protozoa rose to about 10(4)/g. When indigenous protozoa were suppressed by the addition of actidione to the soil, the density of the test rhizobium did not fall initially, but its abundance declined to about 10(7)/g when actidione-resistant protozoa arose in significant numbers. The addition to actidione-treated soil of an antibiotic-resistant strain of Paramecium led to a rapid decrease in the population of the rhizobium, the density reaching essentially the same value as in soil receiving neither the drug nor the paramecia. The same changes occurred with Xanthomonas campestris as test prey except that its numbers fell to about 10(5)/g of soil. These data provide further evidence for the key role of protozoa in controlling the abundance of populations of certain bacteria introduced into soil.

Animals↗

Triacylglycerol and very low density lipoprotein secretion into plasma of squirrel monkeys.

We determined the effects of varying the types and level of dietary fat and cholesterol on the increase in plasma total triacylglycerol concentrations after injection of Triton WR-1339, an inhibitor of lipoprotein lipase, into monkeys that had been subjected to an overnight fast. The monkeys that had been treated with Triton WR-1339 were then given a test meal by intragastric intubation. Dietary cholesterol, high levels of fat and saturated fat in the habitual diet reduced the rate of release of triacylglycerol to plasma in the fasted monkey. We also determined the changes in protein and lipid concentrations of the different lipoprotein fractions. The injection of Triton WR-1339 resulted in a linear increase with time in the concentration of protein and triacylglycerol in the very low density (chylomicron-free and d less than 1.006) lipoproteins, but there was an increase in the ratio of traicylglycerol to protein in that fraction. Most of the increase (96%) in very low density protein was in the B protein. Regardless of the habitual diet, a test meal accentuated the rate of triacylglycerol appearance in whole plasma and in the very low density lipoproteins of Triton WR-1339-treated monkeys, and the rate of increase of the protein component after feeding was slightly higher. Thus the administration of a meal to the fasted Triton WR-1339-treated squirrel monkey further increased the proportion of triacylglycerol in very low density lipoproteins. Although dietary cholesterol and saturated fat in the habitual diet depressed the rate of increase in very low density triacylglycerol during fasting, the rate of protein synthesis was not significantly affected. After administration of a test meal the rates of increase in triacylglycerol and protein in the very low density lipoproteins were similar for monkeys from the different diet groups. Triton WR-1339 administration caused a slight and progressive increase in the intermediate density (d 1.006-1.019) lipoproteins and a marked and progressive decrease in the low density (d 1.019-1.063) lipoproteins. There was an immediate (by 5 min) drop of 70% or more in high density (d 1.063-1.21) lipoprotein protein, but the lipids except triacylglycerol remained unchanged. There was a decrease in both the A (the major fraction) and C proteins. The rates of very low density B protein secretion were comparable to the rates of low density lipoprotein catabolism that had been previously demonstrated for this species.

Animals↗

Chemotherapy of malignant histiocytosis in adults.

Malignant histiocytosis is a fulminant neoplasm resistent to single agent chemotherapy and resulting in death within 6 months. Sixteen patients have received chemotherapy for this disorder between 1965-1975 at Stanford. Nine patients responded to chemotherapy. Responders had a median survival of 23 months from onset of symptoms and a significantly longer survival than non-responders (p = 0.03). The most promising responses were in seven patients treated with a combination of cyclophosphamide, adriamycin, vincristine and prednisone. Five of the seven responded, with two of the five later relapsing and dying, two having equivocal evidence of disease while on chemotherapy for 6 and 9 months, and one free of disease for 17 months after completing 8 months of chemotherapy. Three patients had central nervous system (CNS) relapses, two during peripheral remission. One of these had control of CNS disease with brain irradiation and intrathecal methotrexate, but all three eventually died. It is hoped that with combination chemotherapy and prophylactic CNS treatment, long term disease-free survivals will be achieved.

Adolescent↗

Diurnal variations of serum testosterone levels in intact and gonadectomized male and female rhesus monkeys.

A radioimmunoassay for serum testosterone which does not require chromatographic separation was used to measure the diurnal variations in intact and orchidecomized males and intact and ovariectomized females. The intact male rhesus monkey shows a distinctive diurnal variation in serum levels of testosterone characterized by lower values during the day and a marked increase in the early evening (1900-2200 hr). The testosterone levels remain high throughout most of the lights-off period in the intact male. In contrast to the intact male, the markedly lowered serum levels of testosterone in the orchidectomized male were higher during the day and consistently showed a nadir during the early evening (2000-2200 hr). The evening nadir of testosterone levels was 51.0% lower than the 24-hr mean whereas the maximum serum level was 46.4% higher. A similar circadian pattern of testosterone was seen in both the intact and ovariectomized females. The testosterone values were higher during the day and consistently showed a nadir during the early evening. These results suggest that the adrenal secretion of testosterone varies in a diurnal pattern characterized by an early evening nadir. This adrenal pattern is overshadowed by a much larger gonadal rhythm in the intact male.

Animals↗

Products Formed from Analogues of 1,1,1-Trichloro-2,2-Bis(p-Chlorophenyl) Ethane (DDT) Metabolites by Pseudomonas putida.

Cultures of Pseudomonas putida growing in solutions with diphenylmethane as sole carbon source formed 1,1,1',1'-tetraphenyldimethyl ether. The product was identified by gas chromatography, mass spectrometry, and infrared and nuclear magnetic resonance spectrometry. The formation of benzophenone, benzhydrol, and phenylglycolic acid was established by gas chromatography and mass spectrometry. Similar techniques also revealed that phenylacetic acid was a major metabolite. Resting cell suspensions converted benzhydrol to phenyl-glycolic acid and products tentatively identified as hydroxybenzhydrols and a hydroxybenzophenone. Cell suspensions of the bacterium also converted the tetraphenyldimethyl ether to benzhydrol and benzophenone. Possible pathways for the degradation of these analogues of 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane (DDT) metabolites are discussed.

Journal Article↗

Microbial transformations of selenium.

Resting cell suspensions of a strain of Corynebacterium isolated from soil formed dimethyl selenide from selenate, selenite, elemental selenium, selenomethionine, selenocystine, and methaneseleninate. Extracts of the bacterium catalyzed the production of dimethyl selenide from selenite, elemental selenium, and methaneseleninate, and methylation of the inorganic Se compounds was enhanced by S-adenosylmethionine. Neither trimethylselenonium nor methaneselenonate was metabolized by the Corynebacterium. Resting cell suspensions of a methionine-utilizing pseudomonad converted selenomethionine to dimethyl diselenide. Six of 10 microorganisms able to grow on cystine used selenocystine as a sole source of carbon and formed elemental selenium, and one of the isolates, a pseudomonad, was found also to produce selenide. Soil enrichments converted trimethylselenonium to dimethyl selenide. Bacteria capable of utilizing trimethylselenonium, dimethyl selenide, and dimethyl diselenide as carbon sources were isolated from soil.

Journal Article↗

Resistance of cysts of amoebae to microbial decomposition.

Cyst walls of Acanthamoeba rhysodes, A. palestinensis, A. castellanii, and one other strain of Acanthamoeba contain 36 to 45% protein and 20 to 34% carbohydrate. More than half of the protein in the walls of A. palestinensis, A. castellanii and Acanthamoeba sp. is accessible to and hydrolyzed by protease, and 67 to 69% of the carbohydrate of A. palestinensis and A. rhysodes walls is hydrolyzed by cellulase. The extent of hydrolysis of walls of the other amoebae by these enzymes is appreciably less, and chitinase and beta-1,3-glucanase have no detectable effect. Protease solubilizes 10% or less of the weight of intact cysts, and no solubilization is observed with cellulase. Walls of A. palestinensis are extensively degraded in soil, the activity is less with A. rhysodes, and little attack on the other amoebae occurs. When added to soil, the protozoa excyst and grow for short periods, the trophozoites then die, and chiefly cysts persist thereafter.

Journal Article↗

Resistance of Rhizobium strains to phygon, spergon, and thiram.

Strains of Rhizobium meliloti, Rhizobium sp. nodulating cowpeas, and R. phaseoli derived from cultures susceptible to tetramethylthiuram disulfide (thiram), 2,3-dichloro-1,4-naphthoquinone (phygon), and 2,3,5,6-tetrachloro-p-benzoquinone (spergon), respectively, grew in the presence of high concentrations of the fungicides and converted them to products not toxic to the sensitive rhizobia. The results of chemical assays demonstrated that the pesticides were destroyed by the resistant bacteria but not by the susceptible parent rhizobia. Resting cells of thiram-metabolizing R. meliloti formed large quantities of dimethyldithiocarbamate, dimethylamine, and CS2 from the pesticide. The products were characterized by gas and thin-layer chromatography, colorimetric reactions, and ultraviolet spectrometry. Dimethylamine and CS2 were formed spontaneously from dimethyldithiocarbamate, but the yield was higher in the presence of R. meliloti. The phygon-resistant bacterium converted the fungicide to five metabolites and thereby rendered the chemical nontoxic to a test fungus. The resistant strain of R. phaseoli generated at least one organic product and released about one-third of the chlorine during its detoxication of spergon.

Biodegradation, Environmental↗

Bacterial metabolism of quaternary ammonium compounds.

Of 10 quaternary ammonium compounds tested for biodegradation by the biological oxygen demand technique, only decyl- and hexadecyltrimethylammonium bromides were decomposed by organisms derived from sewage and soil. A mixture consisting of individual strains of Pseudomonas and Xanthomonas grew in solutions containing decyltrimethylammonium bromide as sole carbon source. The xanthomonad metabolized this quaternary ammonium compound in the presence of other organic molecules. The products of this activity included 9-carboxynomyl- and 7-carboxyheptyltrimethylammonium, suggesting that the terminal carbon of the decyl moiety is oxidized and the resulting carboxylic acid is subject to beta-oxidation.

Biodegradation, Environmental↗

Effect of oil composition on both adjuvant-induced arthritis and delayed hypersensitivity to purified protein derivative and peptidoglycans in various rat strains.

We confirmed that, when immunized with a conventional complete Freund adjuvant (water in oil), Lewis rats were highly susceptible to adjuvant arthritis, Fisher rats were less susceptible, and Buffalo rats were much less susceptible. However, mycobacterial delipidated cells in squalane (squalane-type adjuvant) produced severe arthritis with almost 100% incidence even in the less susceptible rat strains except for Buffalo rats. With regard to an immune response, Freund complete adjuvant induced strong delayed hypersensitivity to purified protein derivative (PPD) and peptidoglycan (PG) in all rat strains used, Whereas the squalane-type adjuvant induced these hypersensitivities only in Lewis and Buffalo rats, but not in Fisher and Brown Norway rats. No correlation was found between development of arthritis and delayed hypersensitivity to either PPD or PG, or both. It seems that PPD hypersensitivity may be inherited differently from PG hypersensitivity.

Animals↗