Sagnac interferometer with adaptive nonlinear detection.

We present a Sagnac interferometer that uses a nonlinear adaptive medium for detection. The nonlinearity of the medium being characterized by a finite response time, the detection has a finite frequency bandwidth determining two operational regimes: at low variation rate of the rotation speed the interferometer operates in the slow-light regime, providing a direct measurement of the angular acceleration. For high variation rate of the rotation speed the amplitude of the alternating component of the Sagnac phase shift is instead detected, with the continuous and low-frequency components filtered out by the adaptive nonlinear process in the medium.

Hepatic encephalopathy associated with paratuberculosis in a goat.

A 3-year-old pregnant Nubian goat that was examined because of weight loss, weakness, and change in attitude was determined to be infected with Mycobacterium paratuberculosis. Signs of depressed attitude, trembling, and ataxia were consistent with hepatic encephalopathy, which was confirmed by detection of hyperammonemia. These signs were consistent with histopathologic lesions in the liver and brain. Changes in energy balance and the hypoproteinemia that often develop in goats with paratuberculosis may lead to fat infiltration of the liver, hepatic insufficiency and, ultimately, hepatoencephalopathy.

Streptococcal fibrinous pericarditis and peritonitis in a Vietnamese pot-bellied pig.

An 8-month-old female Vietnamese pot-bellied pig was examined because of a 48-hour history of anorexia and signs of depression. Hypothermia, dehydration, pronounced respiratory effort, and muffled heart sounds were detected. Abdominal ultrasonography revealed ascites and hepatic congestion. Echocardiography revealed pericardial effusion and fibrinous pericarditis. Ultrasound-guided pericardiocentesis was diagnostic and therapeutic. Cytologic examination of pericardial and peritoneal fluid revealed degenerated neutrophils and intra-and extracellular gram-positive cocci. On microbial culture of pericardial and peritoneal fluid specimens, moderate growth of a beta-hemolytic Streptococcus sp of group G was observed. After initial treatment corrected hypothermia and dehydration, the pig was treated with sulfadiazine/sulfamerazine/sulfamethazine and oxytetracycline for 30 days. Echocardiographic examination 3 months after the initial examination revealed resolution of the pericardial effusion and fibrinous pericarditis.

Hemorrhage into the guttural pouch (auditory tube diverticulum) associated with rupture of the longus capitis muscle in three horses.

Three horses were determined to have hemorrhage into a guttural pouch unassociated with mycosis, empyema, neoplasia, or foreign body. The source of the hemorrhage appeared to be the rupture of the longus capitis muscle and its associated vascular supply.

Medical response to catastrophic events: California's planning and the Loma Prieta earthquake.

The threat of a great earthquake has compelled California to develop a disaster plan for catastrophic medical events that calls for local response with state-coordinated mutual aid and casualty evacuation, if necessary. During the 1989 Loma Prieta earthquake that killed 63 people and injured 3,700, local emergency medical services systems were busy but not stressed excessively. The medical mutual aid system delivered medical personnel, supplies, and blood. One hospital suffered severe nonstructural damage, but it was able to treat large numbers of casualties. Our system performed admirably in this limited response, but was hampered by difficulties with disaster intelligence, communications, emergency medical services dispatch, patient care records, hospital damage, and inadequate disaster training. We describe our state's mutual aid system, the Loma Prieta response, and lessons and recommendations for the future.

Glyphosate sensitivity of 5-enol-pyruvylshikimate-3-phosphate synthase from Bacillus subtilis depends upon state of activation induced by monovalent cations.

The 5-enol-pyruvylshikimate-3-phosphate (EPSP) synthase from Bacillus subtilis was activated by monovalent cations, catalytic activity being negligible in the absence of monovalent cations. The order of cation effectiveness (NH4+ greater than K+ greater than Rb+ greater than Na+ = Cs+ = Li+) indicated that the extent of activation was directly related to the unhydrated cation radius. Ammonium salts, at physiological concentrations, were dramatically more effective than other cations. Activation by ammonium was instantaneous, was not influenced by the counter ion, and gave a hyperbolic saturation curve. Hill plots did not show detectable cooperativity in the binding of ammonium. Double-reciprocal plots indicated that ammonium increases the maximal velocity and decreases the apparent Michaelis constants of EPSP synthase with respect to both phosphoenol pyruvate (PEP) and shikimate 3-phosphate (S3P). A direct relationship between sensitivity to inhibition by glyphosate and the activation state of EPSP synthase was demonstrated. Hill plots indicated a single value for glyphosate binding throughout the range of ammonium activation. Double-reciprocal plots of substrate saturation data obtained with ammonium-activated enzyme in the presence of glyphosate showed glyphosate to behave as a competitive inhibitor with respect to PEP and as a mixed-type inhibitor relative to S3P. The increased glyphosate sensitivity of ammonium-activated EPSP synthase is attributed to a lowering of the inhibitor constant of glyphosate with respect to PEP. Erroneous underestimates of sensitivities of some bacterial EPSP synthases to inhibition by glyphosate may result from failure to recognize cation requirements of EPSP synthases.

Differentially Regulated Isozymes of 3-Deoxy-d-arabino-Heptulosonate-7-Phosphate Synthase from Seedlings of Vigna radiata [L.] Wilczek.

Two isozymes of 3-deoxy-d-arabino-heptulosonate-7-phosphate synthase (EC 4.1.2.15) designated DS-Mn and DS-Co were separated from seedlings of Vigna radiata [L.] Wilczek by DEAE-cellulose column chromatography. DS-Mn was activated 2.6-fold by 0.4 millimolar manganese, had an activity optimum of 7.0, and was substrate inhibited by erythrose-4-phosphate (E4P) concentrations in excess of 0.5 millimolar. In contrast, DS-Co had an activity optimum at pH 8.8, required E4P concentrations of at least 4 millimolar to approach saturation, and exhibited an absolute requirement for divalent cation (cobalt being the best). Regulatory properties of the two isozymes differed dramatically. The activity of DS-Mn was activated by chorismate (noncompetitively against E4P and competitively against phosphoenolpyruvate), and was inhibited by prephenate and l-arogenate (competitively against E4P and noncompetitively against phosphoenolpyruvate in both cases). Under standard assay conditions, l-arogenate inhibited the activity of DS-Mn 50% at a concentration of 155 micromolar and was at least 3 times more potent than prephenate on a molar basis. Weak inhibition of DS-Mn by l-tryptophan was also observed, the magnitude of inhibition increasing with decreasing pH. The pattern of allosteric control found for DS-Mn is consistent with the operation of a control mechanism of sequential feedback inhibition governing overall pathway flux. DS-Co was not subject to allosteric control by any of the molecules affecting DS-Mn. However, DS-Co was inhibited by caffeate (3,4-dihydroxycinnamate), noncompetitively with respect to either substrate. The striking parallels between the isozyme pairs of 3-deoxy-d-arabino-heptulosonate-7-phosphate synthase and chorismate mutase are noted-one isozyme in each case being tightly regulated, the other being essentially unregulated.

Glyphosate Inhibition of 5-Enolpyruvylshikimate 3-Phosphate Synthase from Suspension-Cultured Cells of Nicotiana silvestris.

Treatment of isogenic suspension-cultured cells of Nicotiana silvestris Speg. et Comes with glyphosate (N-[phosphonomethyl]glycine) led to elevated levels of intracellular shikimate (364-fold increase by 1.0 millimolar glyphosate). In the presence of glyphosate, it is likely that most molecules of shikimate originate from the action of 3-deoxy-d-arabino-heptulosonate 7-phosphate (DAHP) synthase-Mn since this isozyme, in contrast to the DAHP synthase-Co isozyme, is insensitive to inhibition by glyphosate. 5-Enolpyruvylshikimate 3-phosphate (EPSP) synthase (EC 2.5.1.19) from N. silvestris was sensitive to micromolar concentrations of glyphosate and possessed a single inhibitor binding site. Rigorous kinetic studies of EPSP synthase required resolution from the multiple phosphatase activities present in crude extracts, a result achieved by ion-exchange column chromatography. Although EPSP synthase exhibited a broad pH profile (50% of maximal activity between pH 6.2 and 8.5), sensitivity to glyphosate increased dramatically with increasing pH within this range. In accordance with these data and the pK(a) values of glyphosate, it is likely that the ionic form of glyphosate inhibiting EPSP synthase is COO(-)CH(2)NH(2) (+)CH(2)PO(3) (2-), and that a completely ionized phosphono group is essential for inhibition. At pH 7.0, inhibition was competitive with respect to phosphoenolpyruvate (K(i) = 1.25 micromolar) and uncompetitive with respect to shikimate-3-P (K(i)' = 18.3 micromolar). All data were consistent with a mechanism of inhibition in which glyphosate competes with PEP for binding to an [enzyme:shikimate-3-P] complex and ultimately forms the dead-end complex of [enzyme:shikimate-3-P:glyphosate].

Enzymological basis for herbicidal action of glyphosate.

The effects of 1 millimolar glyphosate (N-[phosphonomethyl]glycine) upon the activities of enzymes of aromatic amino acid biosynthesis, partially purified by ion-exchange chromatography from mung bean seedings (Vigna radiata [L.] Wilczek), were examined. Multiple isozyme species of shikimate dehydrogenase, chorismate mutase, and aromatic aminotransferase were separated, and these were all insensitive to inhibition by glyphosate. The activities of prephenate dehydrogenase and arogenate dehydrogenase were also not sensitive to inhibition. Two molecular species of 3-deoxy-d-arabino-heptulosonate 7-phosphate (DAHP) synthase were resolved, one stimulated several-fold by Mn(2+) (DAHP synthase-Mn), and the other absolutely dependent upon the presence of Co(2+) for activity (DAHP synthase-Co). Whereas DAHP synthase-Mn was invulnerable to glyphosate, greater than 95% inhibition of DAHP synthase-Co was found in the presence of glyphosate. Since Co(2+) is a V(max) activator with respect to both substrates, glyphosate cannot act simply by Co(2+) chelation because inhibition is competitive with respect to erythrose-4-phosphate. The accumulation of shikimate found in glyphosate-treated seedlings is consistent with in vivo inhibition of both 5-enolpyruvylshikimic acid 3-phosphate synthase and one of the two DAHP synthase isozymes. Aromatic amino acids, singly or in combination, only showed a trend towards reversal of growth inhibition in 7-day seedlings of mung bean. The possibilities are raised that glyphosate may act at multiple enzyme targets in a given organism or that different plants may vary in the identity of the prime enzyme target.

Enzymology of l-Tyrosine Biosynthesis in Mung Bean (Vigna radiata [L.] Wilczek).

The enzymes of the 4-hydroxyphenylpyruvate (prephenate dehydrogenase and 4-hydroxyphenylpyruvate aminotransferase) and pretyrosine (prephenate aminotransferase and pretyrosine dehydrogenase) pathways of l-tyrosine biosynthesis were partially purified from mung bean (Vigna radiata [L.] Wilczek) seedlings. NADP-dependent prephenate dehydrogenase and pretyrosine dehydrogenase activities coeluted from ion exchange, adsorption, and gel-filtration columns, suggesting that a single protein (52,000 daltons) catalyzes both reactions. The ratio of the activities of partially purified prephenate to pretyrosine dehydrogenase was constant during all purification steps as well as after partial inactivation caused by p-hydroxymercuribenzoic acid or heat. The activity of prephenate dehydrogenase, but not of pretyrosine dehydrogenase, was inhibited by l-tyrosine at nonsaturating levels of substrate. The K(m) values for prephenate and pretyrosine were similar, but the specific activity with prephenate was 2.9 times greater than with pretyrosine.Two peaks of aromatic aminotransferase activity utilizing l-glutamate or l-aspartate as amino donors and 4-hydroxyphenylpyruvate, phenylpyruvate, and/or prephenate as keto acid substrates were eluted from DEAE-cellulose. Of the three keto acid substrates, 4-hydroxyphenylpyruvate was preferentially utilized by 4-hydroxyphenylpyruvate aminotransferase whereas prephenate was best utilized by prephenate aminotransferase. The identity of a product of prephenate aminotransferase as pretyrosine following reaction with prephenate was established by thin layer chromatography of the dansyl-derivative.

Shifting perspectives on the alcoholism treatment movement 1940--1955.

Relationships between the Yale Center of Alcohol Studies, considered to be representative of the alcoholism treatment movement, and various temperance groups, clergy and spokesmen for the alcoholic beverage industry are examined.