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R L Martin

Publications and source records attributed to R L Martin.

At least 109 records · Page 6Linked to original sources
PubMed1989

Rat liver ATP-sulfurylase: purification, kinetic characterization, and interaction with arsenate, selenate, phosphate, and other inorganic oxyanions.

ATP-sulfurylase (ATP:sulfate adenylyltransferase; EC 2.7.7.4), the first enzyme of the two-step sulfate activation sequence, was purified extensively from rat liver cytosol. The enzyme has a native molecular mass of 122 +/- 12 kDa and appears to be composed of identical 62 +/- 6-kDa subunits. At 30 degrees C and pH 8.0 (50 mM Tris-Cl buffer containing 5 mM excess Mg2+), the best preparations have "forward reaction" specific activities of about 20 and 2 units X mg protein-1 with MoO4(2-) and SO4(2-), respectively. The reverse (ATP synthesis) specific activity is about the same as the forward molybdolysis activity. The kinetic constants under the above conditions are as follows: KmA = 0.21 mM, Kia = 0.87 mM, KmB = 0.18 mM, KmQ = 0.65 microM, Kiq = 0.11 microM, and KmP = 5.0 microM where A = MgATP, B = SO4(2-), Q = APS, and P = total PPi at 5 mM Mg2+. PPi is a mixed-type inhibitor with respect to MgATP and SO4(2-). SeO4(2-) is an alternative inorganic substrate with a Vmax about 20% that of SO4(2-). The product, APSe, is unstable. But in the presence of a sufficient excess of APS kinase, APSe is completely converted to PAPSe. The rate constant for nonenzymatic PAPSe hydrolysis was determined from measurements of the final steady-state reaction rate in the presence of limiting initial SeO4(2-) and a large excess of MgATP, ATP sulfurylase, APS kinase, and the other coupling enzymes and their cosubstrates. The results yielded a k of 2.4 +/- 0.5 X 10(-3) sec-1 (t1/2 ca. 5 min). Phosphate is an effective buffer for enzyme purification and storage but inhibits catalytic activity, particularly at low substrate concentrations. In the presence of buffer levels of Pi, the MgATP reciprocal plot of the SO4(2-)-dependent reaction is concave-up. Inorganic monovalent oxyanions are dead end inhibitors competitive with SO4(2-) and apparently uncompetitive with respect to MgATP. The relative potencies are in the order ClO3- greater than ClO4- greater than FSO3- greater than NO3-. Thiosulfate is also competitive with SO4(2-) but noncompetitive with respect to MgATP. Several divalent oxyanions (MoO4(2-), WO4(2-), CrO4(2-), and HAsO4(2-] promote the enzyme-catalyzed cleavage of MgATP to AMP and MgPPi. The ratio Vmaxf/KmA ranged from 0.7 to 200 for various reactive inorganic substrates. The cumulative results suggest the random binding of MgATP and the inorganic substrate but the ordered release of MgPPi before APS.(ABSTRACT TRUNCATED AT 400 WORDS)

Adenosine Phosphosulfate↗
PubMed1989

Paraquat is not accumulated in B16 tumor cells by the polyamine transport system.

We have examined the effect of difluoromethylornithine on the ability of B16 melanoma cells to take up putrescine and the 4,4'-dipyridyl herbicide paraquat. Pretreatment with difluoromethylornithine for 24 hr enhanced putrescine uptake by inducing the maximum capacity of the transport system without affecting the Km for the substrate. Paraquat uptake was minor compared with that of putrescine and was not affected by difluoromethylornithine. Neither putrescine, spermidine or spermine at concentrations up to 100 microM inhibited the accumulation of paraquat. However, paraquat competitively inhibited putrescine transport (Ki = 54 +/- 10 microM). Exposure of the B16 melanoma cells for 24 hr to increasing concentrations of paraquat produced a dose-dependent inhibition of DNA synthesis. Difluoromethylornithine pretreatment did not affect paraquat toxicity. These data show that paraquat is not taken up into B16 melanoma cells by the uptake system responsible for transporting putrescine. Moreover, it is likely that the difluoromethylornithine inducible polyamine transport system in B16 melanoma cells is characteristically different to that previously described in normal mammalian lung since the latter is reportedly capable of transporting both putrescine and paraquat.

Biological Transport↗
PubMed1989

Interaural sound pressure level differences associated with sound-source locations in the frontal hemifield of the domestic cat.

Interaural sound pressure level differences (ILDs) associated with a range of sound-source azimuths and elevations in the frontal hemifields of four cats were measured for each of seven pure-tone stimuli ranging in frequency from 2-32 kHz. The overall pattern of ILD across location at each frequency was remarkably similar in all cats. At 2, 4 and 8 kHz the relationships of ILD to azimuth and elevation were generally monotonic with ILD increasing with increasing azimuth. At 12 kHz and above, however, non-monotonic relationships developed and circumscribed regions of particularly large, positive and negative ILDs were apparent. That ILDs associated with many sound-source locations on the near side of the head are negative in sign has not been widely noted in the previous literature. The data obtained in this study were compared with those from previous studies and the acoustical mechanisms likely to have contributed to production of the observed ILDs were considered. Some implications of the data for auditory localization in three-dimensional space were discussed.

Air Pressure↗
PubMed1989

Reduction by general anaesthetics of group Ia excitatory postsynaptic potentials and currents in the cat spinal cord.

1. The effects of thiopentone and halothane on excitatory synaptic transmission at group Ia afferent synapses on lumbosacral motoneurones were studied in the anaesthetized or decerebrate cat. 2. Thiopentone (10 mg kg-1) infused on a background of light pentobarbitone anaesthesia caused a decrease in single-fibre monosynaptic group Ia excitatory postsynaptic potentials (EPSPs) of between 0 and 24%. A step increase in inspired halothane concentration in the range 0.7-0.9% produced a decrease in EPSP amplitude of between 0 and 31%. These effects were reversible when the anaesthetic level was reduced. 3. Fluctuation analysis of selected single-fibre group Ia EPSPs revealed that these effects could be accounted for by a decrease in the probability of occurrence of EPSPs of larger amplitude, and an increase in the probability of occurrence of EPSPs of smaller amplitude. The mean separation between discrete amplitudes was not altered by either anaesthetic agent. 4. EPSPs whose time course indicated a somatic site of origin were voltage clamped to study the effect of the anaesthetics on the time course of the synaptic currents. Neither thiopentone nor halothane produced a consistent effect on the time constant of decay of the current, although they both depressed its peak amplitude. 5. The results are interpreted as indicating a presynaptic site of action of both anaesthetics at the concentrations studied: the probability of release of neurotransmitter is reduced, without any detectable change in the mean duration of the postsynaptic conductance increase. These findings are discussed in relation to the mechanisms of action of anaesthetics on exocytosis and presynaptic inhibition.

Animals↗
PubMed1989

Update on dementia of the Alzheimer type.

An estimated three-quarters to one million Americans are in advanced stages of dementia of the Alzheimer type (DAT), numbers that are certain to grow as the population of the United States ages. An explosion in research interest in DAT in the last ten years promises greater understanding of the pathophysiology of the disease and eventual development of effective treatment of characteristic intellectual deficits and behavioral symptoms. The search continues for the underlying cause or causes of the condition and a cure. This article reviews current information about the epidemiology, neuropathologic findings, diagnosis, and treatment of DAT and some of the most promising areas of research.

Aged↗
PubMed1988

The general modifier ("allosteric") unireactant enzyme mechanism: redundant conditions for reduction of the steady state velocity equation to one that is first degree in substrate and effector.

The general unireactant modifier mechanism in the absence of product can be described by the following linked reactions: E + S k1 in equilibrium k-1 ES k3----E + P; E + I k5 in equilibrium k-5 EI; EI + S k2 in equilibrium k-2 ESI k4----EI + P; and ES + I k6 in equilibrium k-6 ESI where S is a substrate and I is an effector. A full steady state treatment yields a velocity equation that is second degree in both [S] and [I]. Two different conditions (or assumptions) permit reduction of the velocity equation to one that is first degree in [S] and [I]. These are (a) that k-2k3 = k-1k4 (Frieden, C., J. Biol. Chem. 239, pp. 3522-3531, (1964)) and (b) that the I-binding reactions are at equilibrium (Reinhart, G. D., Arch. Biochem. Biophys. 224, pp. 389-401 (1983)). It is shown that each condition gives rise to the other (i.e., if the I-binding reactions are at equilibrium, then k-2k3 must equal k-1k4 and vice-versa). If one assumes equilibrium for the I-binding steps, the velocity equation derived by the method of Cha (J. Biol. Chem. 243, pp. 820-825 (1968)) is apparently second degree in [I] (Segel, I. H., Enzyme Kinetics, p. 838, Wiley-Interscience (1975)), but reduces to a first degree equation when the relationship derived by Frieden is inserted. If one starts by assuming a single equilibrium condition for I binding, e.g., k-5[EI] = k5[E][I] or k-6[ESI] = k6[ES][I], then a traditional algebraic manipulation of the remaining steady state equations provides first degree expressions for the concentrations of all enzyme species and also discloses the Frieden relationship.

Binding Sites↗
PubMed1988

A family-genetic study of dementia of Alzheimer type.

A family study of 22 rigorously diagnosed subjects with dementia of Alzheimer type (DAT) and 24 nondemented controls revealed a morbid risk of DAT to first-degree relatives of probands of 41% by age 83 years compared with a risk of 23% by age 85 years in control relatives. Senescent forgetfulness, defined as consistent but not incapacitating memory deficit, may have represented early DAT in some instances. When such cases were included as secondary cases, the morbid risk to first-degree relatives of probands was 67% by age 86 years while risk to comparable control relatives remained 23%. No cases of Down's syndrome were observed. A significant excess of hematologic malignant neoplasms was found among first-degree relatives of probands, supporting an association with DAT. Overall, the findings add further evidence of the action of familial-genetic factors in the etiology of DAT. The magnitude of the effect is consistent with an autosomal dominant mode of inheritance, with penetrance nearly complete by age 85 years. The probands were not selected on the basis of factors posited by some to indicate a familial form of DAT, suggesting that such a genetic mechanism may be involved in the occurrence of DAT in general.

Age Factors↗
PubMed1988

The frequency organization of the inferior colliculus of the guinea pig: A [14C]-2-deoxyglucose study.

The [14C]-2-deoxyglucose (2-DG) technique was used to study the frequency organization of the inferior colliculus (IC) of the guinea pig. Discrete regions of heightened 2-DG labelling were observed in the ICs of animals exposed to a variety of pure-tone stimuli. Regions associated with 1, 4, 10 and 19 kHz pure tones were described and displayed in three-dimensional representations. The IC of the guinea pig was found to be arranged as a series of sheet-like, iso-frequency planes that extend throughout the nucleus from its caudal to its rostral pole. Iso-frequency planes associated with low frequencies are located dorsolaterally in the nucleus and those associated with higher frequencies are located progressively more ventromedially. The predominant orientation, in the frontal plane, of all iso-frequency planes is oblique from dorsomedial to ventrolateral. Most planes, however, twist about their caudal-to-rostral axis in a caudal-to-rostral, horizontal-to-vertical direction. The extent to which each plane twists is frequency-dependent; planes associated with low frequencies twist most and those associated with high frequencies do not twist at all.

Acoustic Stimulation↗
PubMed1987

ATP sulfurylase from Penicillium chrysogenum. Molecular basis of the sigmoidal velocity curves induced by sulfhydryl group modification.

ATP sulfurylase from Penicillium chrysogenum is a noncooperative homooligomer containing three free sulfhydryl groups per subunit. Under nondenaturing conditions, one SH group per subunit was modified by 5,5'-dithiobis-(2-nitrobenzoate), or N-ethylmaleimide. Modification had only a small effect on kcat, but markedly increased the [S]0.5 values for the substrates, MgATP and SO4(2-). MgATP and adenosine-5'-phosphosulfate protected against modification. The SH-modified enzyme displayed sigmoidal velocity curves for both substrates with Hill coefficients (nH) of 2. Fluorosulfonate (FSO3-) and other dead-end inhibitors competitive with SO4(2-) activated the SH-modified enzyme at low SO4(2-) concentration. In order to determine whether the sigmoidicity resulted from true cooperative binding (as opposed to a kinetically based mechanism), the shapes of the binding curves were established from the degree of protection provided by a ligand against phenylglyoxal-dependent irreversible inactivation under noncatalytic conditions. Under standard conditions (0.05 M Na-N-(2-hydroxyethyl)piperazine-N'-3-propanesulfonic acid buffer, pH 8, 30 degrees C, and 3mM phenylglyoxal) the native enzyme was inactivated with a k of 2.67 +/- 0.25 X 10-3 s-1, whereas k for the SH-modified enzyme was 5.44 +/- 0.27 X 10-3 s-1. The increased sensitivity of the modified enzyme resulted from increased reactivity of ligand-protectable groups. Both the native and the SH-modified enzyme displayed hyperbolic plots of delta k (i.e. protection) versus [MgATP], or [FSO3-], or [S2O3(2-]) in the absence of coligand (nH = 0.98 +/- 0.06). The plots of delta k versus [ligand] for the native enzyme were also hyperbolic in the presence of a fixed concentration of coligand. However, in the presence of a fixed [FSO3-] or [S2O3(2-]), the delta k versus [MgATP] plot for the SH-modified enzyme was sigmoidal, as was the plot of delta k versus [FSO3-] or [S2O3(2-]) in the presence of a fixed [MgATP]. The nH values were 1.92 +/- 0.09. The results indicate that substrates (or analogs) bind hyperbolically to unoccupied SH-modified subunits, but in a subunit-cooperative fashion to form a ternary complex.

Adenosine Triphosphate↗
PubMed1987

The auditory spatial acuity of the domestic cat in the interaural horizontal and median vertical planes.

The auditory spatial acuity of the domestic cat in the interaural horizontal plane was examined using broadband noise and nine pure-tone stimuli ranging in frequency from 0.5 to 32 kHz. Acuity in the median vertical plane was also examined using broadband noise and three pure tones of frequencies 2, 8 and 16 kHz. Minimum audible angles (MAAs) for a reference source directly in front of an animal were measured in the horizontal plane for five cats and in the vertical plane for four. The smallest MAAs measured were those for the noise stimulus, for which MAAs in the horizontal and vertical planes were similar in magnitude. Horizontal plane MAAs for low-frequency tones were smaller than those for high, and the pattern of MAA change with frequency was consistent with the use of interaural phase and sound pressure level difference cues to localize low- and high-frequency tones, respectively. Three of the four cats trained on the vertical plane MAA task did not achieve criterion performance for any of the three pure tones, and the MAAs obtained from the fourth cat at each frequency were relatively large. Vertical plane performance was consistent with the use of spectral transformation cues to discern the elevation of a complex stimulus.

Animals↗
PubMed1987

The representation of stimulus azimuth by high best-frequency azimuth-selective neurons in the central nucleus of the inferior colliculus of the cat.

The responses to changes in stimulus azimuth of 220 high best-frequency (BF) (greater than 3 kHz) units in the central nucleus of the inferior colliculus of the anesthetized cat were studied with BF tones (220 units) and noise stimuli (84 units). By this means we hoped to gain some insights into the way the azimuthal locations of high BF stimuli were represented in the inferior colliculus. For each unit the discharge rate was determined for stimuli located along a plane tilted at 20 degrees above the horizontal. This plane was chosen to optimize pinna directionality. Locations in the frontal field were sampled in 10-20 degree steps around a 170 degree arc. These measurements were repeated at a number of different stimulus intensities until the directional properties of the unit became clear. Units for which the functions relating discharge rate to azimuth for a given stimulus showed a clear feature (peak or border), the azimuthal location of which varied little with intensities between 20 and 40 dB above threshold, were defined as being azimuth selective for that stimulus. Only 13% of units were azimuth selective for BF tones, whereas 44% were selective for noise. Many azimuth functions for selective units were of the plateau-shaped type for which relatively high discharge rates occurring at most contralateral azimuths declined steeply to near zero and remained low for most ipsilateral azimuths. These plateau-shaped functions were most common for tonal stimuli. Other functions showed a fixed azimuth of maximum firing (best azimuth); these were more common for noise than for tonal stimuli. Detailed azimuth functions for both tone and noise stimuli were measured for 63 units. Some exhibited the same kind of azimuth function to both stimuli. However, 18 units were azimuth selective to noise but not to tones. The borders of plateau-shaped functions obtained using both noise and tonal stimuli were concentrated within 20 degrees of the median plane. Very few units had borders that spanned peripheral ipsilateral or contralateral azimuths. Although the best azimuths of some noise azimuth functions were observed to lie at these peripheral azimuths, the majority occurred around 20 degrees contralateral to the median plane. The recording sites for units were related to a three-by-three matrix of rostrocaudal and mediolateral locations across the central nucleus. Units that were azimuth selective to noise were distributed fairly evenly throughout the central nucleus, whereas units azimuth selective to tones formed highest proportions rostrally.(ABSTRACT TRUNCATED AT 400 WORDS)

Acoustic Stimulation↗
PubMed1986

Visual pigment homologies revealed by DNA hybridization.

A bovine rhodopsin complementary DNA probe was used to detect homologous visual pigment genes in a variety of species. Under stringent DNA hybridization conditions, genomic DNA from most vertebrate species carried a single homologous fragment. Additional homologies were detected in some vertebrates by reducing the hybridization stringency. Homologous fragments were also detected in DNA isolated from invertebrate species, a unicellular alga, and an archaebacterium; many of these fragments were homologous to a Drosophila opsin probe. These results suggest that photosensory pigments in a wide variety of species arose from a common precursor.

Animals↗
PubMed1986

Diastolic flow as a predictor of arterial stenosis.

With a pulsed Doppler imaging system, it is now possible to interrogate sites from the aorta to the popliteal trifurcation. To determine which velocity parameters could be correlated with the degree of disease as determined by angiography, 34 arterial stenoses identified by scanning were also evaluated by contrast arteriography and classified in 10% increments. The angiographic readings were blinded with respect to the scan results. Four hand-measured parameters from velocity waveforms obtained at the site of stenosis were correlated with the angiogram--peak systolic velocity, systolic rise time, diastolic reverse velocity, and diastolic reverse flow time. When diastolic reverse flow was absent, diastolic forward flow was recorded. To describe diastolic flow along a continuum, diastolic reverse velocity was ascribed a positive value and diastolic forward velocity was ascribed a negative value. A systolic velocity gradient (peak velocity/rise time) was also calculated. The relationship between the angiographic categories and the measured parameters was evaluated with the Jonkheere-Terpstra trend test. A trend was determined with diastolic flow (diastolic reverse flow or diastolic flow velocity) that was significant (p less than 0.01). The linear regression was calculated (y = 40.8 + [-5.6X]), and correlation coefficient was obtained (r = 0.76) that was statistically significant (p less than 0.01). The method enables mapping and calculation of arterial stenoses by noninvasive means. This can be expected to obviate the need for diagnostic angiograms in certain and select cases in which angioplasty can be expected to be beneficial. It also affords a convenient quantitative means of following lesions over time.

Angiography↗
PubMed1986

Use of hemodynamic parameters in the diagnosis of mesenteric insufficiency.

To evaluate the hemodynamic characteristics of the normal mesenteric circulation, five parameters of the velocity waveforms were measured in 15 normal subjects in the celiac and superior mesenteric arteries (SMA) in the pre- and postprandial periods. It was noted that changes in celiac artery flow after eating was minimal, indicating that this vessel's major supply function is not to the gut. SMA parameters showing the most significant and consistent changes after a meal were the diastolic reverse flow and diastolic forward flow (DFF). Four patients referred with symptoms of intestinal angina underwent scanning and subsequent angiography of their mesenteric circulation. All four exhibited loss of reverse flow in the SMA. The change in DFF in the SMA was statistically significant (p = 0.01). Change in peak systolic velocity in the celiac artery was marginally significant (p = 0.05). Angiography revealed that three patients had greater than 90% stenosis of both vessels. The fourth patient had a 90% celiac artery and 65% SMA stenosis. The technique described offers the first noninvasive means of identifying mesenteric insufficiency. It is an effective screening method for a disease entity difficult to verify without selective arteriography. The use of velocity waveform parameters giving good discrimination between normal subjects and those with stenoses of the visceral arteries should reduce both the incidence of missed diagnosis and unnecessary angiography.

Adult↗
PubMed1986

Noninvasive diagnosis of renal artery stenosis by ultrasonic duplex scanning.

We retrospectively studied the results of duplex scanning for evaluation of renal artery disease in 158 patients. Satisfactory examinations were achieved in 144 patients (90%). Arteriograms were available for 43 renal arteries. We used the ratio of the peak velocities in the renal artery and the aorta (RAR) to separate nonstenotic arteries (less than 60% diameter reduction) from stenotic arteries (greater than 60% diameter reduction). With an RAR of greater than 3.5 to indicate stenotic lesions, duplex scanning had a sensitivity of 91% (20 of 22 diseased arteries correctly identified) and specificity of 95% (20 of 21 normal or insignificantly diseased arteries correctly identified). One of four occluded arteries was incorrectly interpreted as patent because of misidentification of a collateral vessel. Prospective studies will be necessary to validate this test and establish other criteria for a more detailed classification of renal artery stenosis. The ratio of the end-diastolic to peak systolic velocities in the renal artery (EDR) tended to decrease with increasing serum creatinine levels, presumably because renal vascular resistance increases with end-stage parenchymal disease. EDR may prove useful in the detection of advanced parenchymal disease before renal artery revascularization is attempted.

Aorta, Abdominal↗