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K Hill

Publications and source records attributed to K Hill.

At least 127 records · Page 7Linked to original sources
PubMed1989

Assessing applicants to the NASA flight program for their renal stone-forming potential.

Spaceflight could provoke formation of kidney stones, in part by causing hypercalciuria and hyperphosphaturia. Applicants for spaceflight who have metabolic or environmental derangements to begin with might be particularly susceptible to stone formation in space. We, therefore, analyzed 24-h urine samples for stone-forming risk factors in 104 male applicants before their selection into the astronaut-mission specialist corps. The urinary environment was abnormally supersaturated with calcium oxalate in 25.0% of applicants, brushite in 36.5%, and monosodium urate in 66.3%, predisposing these applicants to crystallization of stone-forming calcium salts. This high level of supersaturation was caused by both "metabolic" and environmental disturbances. Thus, hypercalciuria was found in 11.5% of applicants, hyperoxaluria in 2.9%, hyperuricosuria in 18.3% and hypocitraturia in 5.8%. Environmental derangements were generally more prominent, as indicated by low urine volume of less than 2 L.d-1 in 84.6%, high urinary phosphate in 24.4%, and high urinary sodium in 10.6% of applicants. The results suggest that most of the abnormal stone risk factors disclosed among applicants for spaceflight programs were environmental in origin.

Adult↗
PubMed1988

Rationale for engineering an enzyme by introducing a mutation that compensates for a deletion.

Procedures are needed for the manipulation of enzymes to introduce improved catalytic efficiencies and substrate affinities, even in the absence of information on three-dimensional structure. We previously described a selection for amino acid replacements that compensate for a large polypeptide deletion in an enzyme. The rationale is that, because of the missing polypeptide sequence, compensatory replacements must create new enzyme-substrate contacts that are not present in the native protein. Here we introduce into an undeleted enzyme a mutation that compensates for a large deletion in the same enzyme. Binding and kinetic measurements show that this mutation has the same effect on the undeleted as on the deleted protein. The results suggest that a new enzyme-substrate interaction has been created by the mutation and that its contribution to the interaction energy is similar in both the deleted and undeleted molecules. Introduction of this class of mutations into enzymes may in general be useful for engineering them to have improved interactions with ligands and substrates.

Alanine-tRNA Ligase↗
PubMed1988

Modulation by calcium of the inhibitor activity of naturally occurring urinary inhibitors.

The possibility that hypercalciuria could cause calcium stone formation through a mechanism other than by increasing urinary saturation of stone-forming calcium salts was explored. The effect of increasing calcium concentration on the inhibitor activity against the spontaneous precipitation of calcium oxalate was examined in whole urine (in the presence of naturally occurring inhibitors) and in synthetic media (with added inhibitors). In 11 patients with calcium nephrolithiasis, the induced hypercalciuria from calcium supplementation (600 mg/day) caused a significant fall in the urinary inhibitory activity against calcium oxalate precipitation, as shown by a decline in the formation product ratio from 12.6 +/- 1.1 SEM to 9.6 +/- 1.4 (P less than 0.005). In order to more fully explore this observation, the effect of increasing calcium concentration on the inhibitory activities of citrate (2 mM), chondroitin sulfate (0.05 mg/liter) and a heterogeneous group of naturally-occurring urinary inhibitors (1.0 mg/liter) against calcium oxalate precipitation was examined in vitro in synthetic solutions. The inhibitory actions of both citrate and chondroitin sulfate were significantly attenuated by increasing calcium concentration from 0.25 mM to 6.0 mM (P less than 0.01). However, raising the calcium concentration in synthetic media containing a mixture of partially purified urinary inhibitors produced a significant rise in the urinary inhibitory activity of this macromolecular mixture (P less than 0.01). We conclude that hypercalciuria can attenuate the inhibitory activities of citrate and chondroitin sulfate against calcium oxalate precipitation while at the same time accentuating the inhibitory activity of naturally-occurring urinary inhibitors.(ABSTRACT TRUNCATED AT 250 WORDS)

Calcium↗
PubMed1988

Transcriptional regulation of a promoter in the men gene cluster of Bacillus subtilis.

The control of men gene expression during growth and sporulation of Bacillus subtilis was examined at the transcriptional level. Two different approaches were used. (i) Steady-state levels of men-specific mRNA were measured directly. (ii) A men'-lacZ gene fusion was constructed. In both cases, it was observed that men promoter activity was maximal at the onset of sporulation and declined soon thereafter. These kinetics were similar to the pattern of menaquinone accumulation previously observed. Expression from the men promoter was independent of the presence of the products of the spo0A and spo0H genes and was enhanced by addition of glucose and glutamine to the culture medium. DNA sequence analysis of the promoter region revealed a potential recognition site for the principal vegetative form of RNA polymerase but not for any of the known minor polymerase forms. The functionality in vivo of the promoter sequence was confirmed by high-resolution S1 nuclease mapping of the transcript start site. An additional sequence element was identified that is shared by the sdhA, citG, and ctaA promoters and may indicate a common regulatory mechanism in the expression of these genes.

Bacillus subtilis↗
PubMed1988

Effect of prolonged bedrest on the propensity for renal stone formation.

The effect of prolonged bedrest immobilization on urinary risk factors for stone formation and on the propensity for the crystallization of calcium salts was examined in eight normal subjects. During 5 weeks of bedrest, the mean urinary calcium excretion rose during the first week and remained elevated (from 5.68 to approximately 7.50 mmol/day). Mean urinary phosphorus excretion increased by the second week of bedrest and remained elevated (from 2.70 to approximately 30.6 mmol/day). Urinary sodium and uric acid excretion rose slightly, as did urinary magnesium. Urinary pH, oxalate, and citrate changed slightly or not at all. Owing to these biochemical alterations, urinary saturation of calcium phosphate, calcium oxalate, and monosodium urate increased significantly during bedrest, but that of uric acid did not change. The inhibitor activity against the spontaneous nucleation of brushite (CaHPO4.2H2O) and calcium oxalate was not altered significantly by bedrest. Thus, the propensity for the crystallization of stone-forming calcium salts was enhanced by bedrest, suggesting that immobilization may confer increased risk for the formation of calcium-containing renal stones.

Adult↗
PubMed1988

Experimental studies on the neurocardiovascular effects of urapidil.

The major purpose of our study was to determine whether urapidil acts in the central nervous system (CNS) to lower arterial blood pressure. Once demonstrating a CNS antihypertensive action of urapidil we further set out to determine: (1) the relative role of a CNS antihypertensive action to the total antihypertensive effect of urapidil; (2) the brain site of action for the antihypertensive effect of urapidil; and, (3) the receptor mechanism whereby urapidil acts in the CNS to lower arterial blood pressure. Studies were conducted in chloralose-anaesthetised cats, and arterial blood pressure and heart rate were monitored. Drugs were administered intravenously (IV), into the cerebral ventricles (ICV), topically by application to the ventral surface of the medulla and by microinjection into specific nuclei. Receptor binding studies were also conducted using rat cerebral cortex homogenates. We found that injection of urapidil into the fourth ventricle decreased arterial pressure. Local application of urapidil to the ventral medullary surface also decreased arterial blood pressure. Microinjection of urapidil into one of the nuclei associated with the ventral surface of the medulla, the rostral part of the nucleus reticularis lateralis (rLRN), produced a similar degree of antihypertensive effect. The effect of urapidil was not altered by alpha 1-receptor blockade. Instead, the urapidil effect resembled that produced by drugs that stimulate serotonin (5-hydroxytryptamine)-1A receptors (B695-40 and 8-OH-DPAT). Furthermore, urapidil was found to have the highest potency for binding to serotonin-1A receptor sites (as compared to alpha 1- and alpha 2-receptor sites). Urapidil administered IV was shown to lower arterial blood pressure in part by blocking peripheral alpha 1-adrenoceptors but also, in high doses, by acting in the CNS to decrease central sympathetic outflow. These data indicate that urapidil is a unique drug, possessing both peripheral and CNS actions which contribute to its antihypertensive effect. Urapidil may also be unique in that its central action may involve activation of serotonin-1A receptors.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1987

Expression of alfalfa mosaic virus RNA 4 in transgenic plants confers virus resistance.

Agrobacterium-mediated transfer from a binary vector was used to produce transgenic Nicotiana tabacum plants that expressed coat protein of the plant virus, alfalfa mosaic virus (AMV). Expression levels of the chimeric gene, which was under the control of the cauliflower mosaic virus 19S promoter, were determined in primary transformed plants, in the progeny from self-fertilization and in the progeny from crosses to normal tobacco. RNA transcripts that were of the expected size as well as a protein of the M(r) and antigenicity of AMV coat protein accumulated in the transgenic plants. Plants that expressed the highest levels of coat protein developed fewer primary infections following inoculation with two strains of AMV and developed systemic infection slower than did plants that did not express coat protein. Resistance was specifically against virions of the AMV strains. AMV RNA and the unrelated virus, tobacco mosaic virus, were as infectious on progeny that expressed coat protein as they were on progeny that did not. The relationship between the virus resistance expressed by these transgenic plants and that observed in virus cross-protection is discussed.

Journal Article↗
PubMed1987

Inhibition by citrate of spontaneous precipitation of calcium oxalate in vitro.

Effect of citrate on the spontaneous precipitation of calcium oxalate was examined in synthetic media. Citrate significantly increased the formation product of calcium oxalate. This "direct" measure of inhibitor activity, representing activity product at the point of nucleation, rose by 76% by the addition of citrate sufficient to provide trivalent citrate concentration of 1.49 mM. Moreover, citrate inhibited calcium oxalate crystallization by complexing calcium and lowering calcium oxalate saturation. This "indirect" measure of inhibitor activity was assessed from the concentration product of calcium oxalate at the point of nucleation, since this measure should provide a reflection of both ion pair formation and direct inhibitor activity of citrate. The concentration product exceeded the formation product at all ionic (trivalent) citrate concentrations, particularly at high ionic citrate levels. At the ionic citrate concentration of 1.49 mM, the rise in the concentration product was 373%, which was nearly fivefold that observed for the formation product. The presence of ferric or aluminum cations at a physiologic concentration of 2 mg/l did not modify the increase in formation product produced by citrate. Thus, citrate inhibits calcium oxalate crystallization, largely by complexing citrate, but also by directly affecting nucleation. Presence of ferric or aluminum cations at a physiological concentration does not modify the inhibitor action of citrate.

Calcium Oxalate↗
PubMed1987

New approaches to the estimation of migration flows from census and administrative data sources.

Census data represent an important source of information about migration flows. However, existing estimation procedures based on intercensal projection are often inconvenient to apply and are sensitive to even quite small changes in enumeration completeness. 2 new estimation procedures applicable to data from 2 censuses are developed and illustrated using US data. The 1st method is essentially a modification of traditional intercensal projection techniques, but as a result of working with age groups rather than cohorts, it is simpler to apply and allows mortality of the migrants to be incorporated over the intercensal period. The 2nd method also uses information from 2 censuses, but also uses independent information on the age pattern of migration from administrative sources or from other census questions. The method uses the fact that the age pattern of recent migration is likely to be different from the age distribution of the overall population to distinguish between intercensal change due to migration and apparent intercensal change due to changes in enumeration completeness. If the method's assumptions are met, it is possible to estimate the relative coverage of the 2 censuses as well as the scale of the independent age pattern of migration relative to the coverage of 1 or other of the censuses. The illustrative applications of the methods to US data suggest that both can work reasonably well.

Age Factors↗
PubMed1987

Hypotensive effect of urapidil: CNS site and relative contribution.

The purposes of our study were to determine the contribution of the CNS to the hypotensive effect of urapidil in the cat and the specific brain site of action of this agent. For the first purpose, urapidil was studied on preganglionic sympathetic nerve activity, arterial pressure, and heart rate. Three systemic bolus doses of urapidil were administered (0.22, 0.44, and 1.3 mg/kg). All three doses lowered arterial pressure, and the highest dose produced a significant decrease in sympathetic nerve discharge in five of six animals studied. The lower two doses had no significant effect on sympathetic activity, and none of the doses altered heart rate. These results suggest that a high i.v. dose of urapidil is required to evoke hypotension by an action in the central nervous system (CNS). For the second purpose, urapidil was applied bilaterally to the intermediate area of the ventral surface of the medulla in doses of 25 and 50 micrograms. These doses caused decreases in arterial pressure of -6.1 +/- 2.2 (p less than 0.05) and -21.0 +/- 5.9 (p less than 0.05) mm Hg, respectively, but no change in heart rate. In addition, respiratory stimulation also occurred with the higher dose as respiratory minute volume increased by 81 +/- 14 ml/min (p less than 0.05). The highest dose of urapidil had no effect on arterial pressure when applied to other chemosensitive areas of the ventral surface of the brain. Comparative studies with prazosin (10 micrograms applied bilaterally to the intermediate area) indicated no hypotensive effect of this alpha 1-adrenoceptor blocking agent.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

[Leiomyosarcoma of the uterus in young identical twins].

The authors describe the occurrence of a confirmed leiomyosarcoma and a tumor suspected of being a leiomyosarcoma in 23-year-old twin sisters. In one of them the tumor had caused clinical symptoms; in the second it was detected at the presymptomatic stage as a result of increased attention after detection of the first tumor. In the first case treatment consisted in an extended abdominal hysterectomy, sparing one ovary, with bilateral interiliac lymph node extirpation; in the second case, in an extended abdominal hysterectomy with both adnexae and bilateral interiliac lymph node extirpation. So far - 13 and 10 months after the initial treatment, respectively - there are no signs of continued tumor growth in either case.

Adult↗