Characterization of Wheat-Triticale Lines Resistant to Powdery Mildew, Stem Rust, Stripe Rust, Wheat Curl Mite, and Limitation on Spread of WSMV.

High yield potential and the wide adaptability of wheat-rye T1BL·1RS translocation lines are attractive to breeders. The wheat-rye lines Lankao 1, 3, 4, and 5 were resistant to a wide spectrum of wheat powdery mildew (Blumeria graminis f. sp. tritici) isolates from both China and Canada. They also were resistant to a mixture of wheat stem rust (Puccinia graminis f. sp. tritici) pathotypes (98WSR) and wheat stripe rust (P. striiformis f. sp. tritici) races from western Canada and China. Colonization of wheat curl mite (WCM) (Aceria tosichella) resulted in slower development of rolling and trapping leaves in the Lankao lines than in the WCM-susceptible check cultivars. The delayed development of Wheat streak mosaic (WSM) symptoms on Lankao lines was observed when transmitted by viruliferous WCM, even though they were susceptible to Wheat streak mosaic virus (WSMV). This effect of Lankao lines on limiting the spread of WSM was comparable with other known sources of WCM resistance. Sequential C-banding and genomic in situ hybridization analyses revealed the presence of a pair of T1BL·1RS translocated chromosomes in the Lankao lines. Segregation analysis of the F2 progeny plants derived from crosses between Lankao 4 and the susceptible wheat cvs. Mingxian 169 and Lovrin 13 indicated that a single dominant gene was responsible for the isolate-specific resistance against wheat powdery mildew in Lankao 4. Polymerase chain reaction analysis using an STS marker amplified rye chromatin in powdery mildew-resistant and -susceptible F2 plants of the Mingxian 169 × Lankao 4 cross demonstrated that the resistance of Lankao 4 was not controlled by a gene or genes located on the rye chromosome arm of T1BL·1RS. The resistance of the Lankao lines to diseases and limitation of the spread of WSMV, in combination with good quality and high yield potential, makes them useful for wheat improvement and production.

Molecular cytogenetic discrimination and reaction to wheat streak mosaic virus and the wheat curl mite in Zhong series of wheat--Thinopyrum intermedium partial amphiploids.

Thinopyrum intermedium (2n = 6x = 42, JJJsJsSS) is potentially a useful source of resistance to wheat streak mosaic virus (WSMV) and its vector, the wheat curl mite (WCM). Five partial amphiploids, namely Zhong 1, Zhong 2, Zhong 3, Zhong 4, and Zhong 5, derived from Triticum aestivum x Thinopyrum intermedium crosses produced in China, were screened for WSMV and WCM resistance. Zhong 1 and Zhong 2 had high levels of resistance to WSMV and WCM. The other three partial amphiploids, Zhong 3, 4, and 5, were resistant to WSMV, but were susceptible to WCM. Genomic in situ hybridization (GISH) using a genomic DNA probe from Pseudoroegneria strigosa (SS, 2n = 14) demonstrated that two partial amphiploids, Zhong 1 and Zhong 2, have almost the identical 10 Th. intermedium chromosomes, including four Js, four J, and two S genome chromosomes. Both of them carry two pairs of J and a pair of Js genome chromosomes and two different translocations that were not observed in the other three Zhong lines. The partial amphiploids Zhong 3, 4, and 5 have another type of basic genomic composition, which is similar to a reconstituted alien genome consisting of four S and four Js genome chromosomes of Th. intermedium (Zhong 5 has two Js chromosomes plus two Js-W translocations) with six translocated chromosomes between S and Js or J genomes. All three lines carry a specific S-S-Js translocated chromosome, which might confer resistance to barley yellow dwarf virus (BYDV-PAV). The present study identified a specific Js2 chromosome present in all five of the Zhong lines, confirming that a Js chromosome carries WSMV resistance. Resistance to WCM may be linked with J or Js chromosomes. The discovery of high levels of resistance to both WSMV and WCM in Zhong 1 and Zhong 2 offers a useful source of resistance to both the virus and its vector for wheat breeding programs.

Different Reactions to the Wheat Curl Mite and Wheat streak mosaic virus in Various Wheat-Haynaldia villosa 6V and 6VS Lines.

Wheat curl mite (WCM), Aceria tosichella, is the vector of Wheat streak mosaic virus (WSMV), a destructive viral pathogen in wheat (Triticum aestivum). Genetic resistance to WCM colonization can reduce the incidence of wheat streak mosaic. Chromosome 6V in Hay-naldia villosa is a new source of WCM resistance. We compared variation in resistance among different sources of H. villosa chromosome 6V and 6VS lines to WCM and WSMV and their effectiveness in controlling the incidence of WSMV following exposure to viruliferous WCM. WCM resistance varied among the 6V and 6VS lines depending on the H. villosa parent. The 6V substitution lines Yi80928, GN21, and GN22 derived from an accession of H. villosa from China, and the 6VS translocation lines 92R137, 92R178, and Sub6V from an H. villosa accession collected from the United Kingdom were uniformly resistant to WCM colonization. In contrast, the 6V substitution line RW15 and a 6VS translocation line Pm33 developed from an H. villosa collection from the former Union of Soviet Socialist Republics were susceptible to WCM. All 6V and 6VS lines were susceptible to WSMV when manually inoculated. However, symptom expression was delayed in the WCM-resistant 6V and 6VS lines after exposure to viruliferous WCM. The 6V and 6VS lines differed in their ability to control WSMV infection. WCM-susceptible lines RW15 and Pm33 had no effect on controlling the infection by WSMV. Lines GN21 and GN22 were the most effective of the three H. villosa sources in limiting the spread of WSMV. Their high yield potential and protein content, in combination with resistance to stripe rust (Puccinia striiformis f. sp. tritici) and powdery mildew (Erysiphe graminis f. sp. tritici), make GN21 and GN22 promising sources of WCM resistance.

Pharmacokinetics, pharmacodynamics, and dose-response relationship of repaglinide in type 2 diabetes.

BACKGROUND: The pharmacodynamics and dose-response relationship of repaglinide, a novel oral hypoglycemic agent, were evaluated in steady-state treatment of patients with type 2 diabetes. METHODS: Efficacy of repaglinide (0.25 mg, 0.5 mg, 1 mg, 2 mg, and 4 mg) was compared to that of placebo in a double-blind, randomized, parallel-group, 4-week dose-response clinical trial in 143 patients. Repaglinide was administered 15 minutes before meals (breakfast, lunch, and dinner). Efficacy of repaglinide therapy was assessed by measuring changes from baseline in mean levels of blood glucose (BGmean), fasting serum glucose (FSG), and mean levels of serum insulin (INSmean). RESULTS: Blood concentrations of repaglinide were proportional to the dose administered. INSmean values increased in all repaglinide treatment groups (by 6.7 to 12.9 microU/mL). All doses of repaglinide significantly decreased values of BGmean and FSG as compared with the placebo group. BGmean values stabilized between the second and third week of repaglinide treatment. A well-defined dose-response relationship was observed for BGmean and FSG values. All doses of repaglinide were well tolerated, and there were no serious adverse events. CONCLUSIONS: These findings show that the therapeutic reduction of serum glucose levels produced by repaglinide is dose-dependent for the 0.25- to 4-mg dose range. All doses of repaglinide tested were effective and well tolerated in patients with type 2 diabetes.

Diabetic neuropathy: a clinical, laboratory and electrodiagnostic study.

The objective of this study was to determine the relationship between nerve conduction velocity (NCV) and hyperglycemia and to assess the extent of NCV changes in adult-onset diabetic patients before and after diabetic treatment. Twenty-five diabetic males (mean age = 50.9 years) were tested twice prior to beginning diabetic treatment. Eighteen of these 25 were also tested at 1, 3, 6, and 12 months after initiation of therapy. Both groups were compared to 23 age-matched controls. Each test session consisted of NCV and clinical sensory and blood chemistry testing. The findings revealed that, before treatment average NCVs of the median, peroneal sural, and tibial nerves and H-reflex latency results were all significantly impaired in diabetic subjects (p less than 0.025). No difference was found between right and left NCVs of the same nerve (p less than 0.05) and NCVs in the lower as well as the upper extremities were significantly reduced (p less than 0.05). Thus, it appears that the neuropathy in these patients was symmetrical and diffuse. Peroneal and median motor nerves showed the greatest amount of NCV slowing when compared to normal values. Furthermore, median, peroneal, and tibial motor NCVs and H-reflex latencies correlated significantly with the degree of hyperglycemia in diabetic subjects before treatment. After initiation of diabetic treatment, median motor NCVs after 1, 3, 6 and 12 months showed significantly improvement when compared to baseline NCV values (all p less than 0.05). Also, the improvement in median NCVs after 3 and 13 months and peroneal NCV after 3 months directly correlated to decreased fasting plasma glucose levels (p less than 0.05).

The regulation of glucose-induced insulin secretion by pre-stimulus glucose level and tolbutamide in normal man.

The relationship between the pre-stimulus glucose level and immunoreactive insulin responses to a glucose challenge (20-g IV) was studied in normal subjects. When the steady-state pre-stimulus glucose concentration was lowered by a 0.33 mU.kg-1.min-1 insulin infusion or raised by a 900 mg/min glucose infusion, no effect on first phase insulin secretion (mean delta 3-5 min insulin level) was observed. In contrast, the second phase response (10-60 min insulin area after glucose pulse) to intravenous glucose fell during insulin infusion and increased during the glucose infusion. Overall, a linear relationship was found between the change of pre-stimulus glucose or level from the control to that during the insulin or glucose infusion and the change in second phase response (r = 0.65, n = 14, p less than 0.02). The effect of tolbutamide infusion (7 mg.m-2.min-1) when compared with saline control was to increase both first phase (+54 +/- 13 mU/l, n = 8, p less than 0.001, mean +/- SEM) and second phase (+972 +/- 256 mU. min-1.l-1, p less than 0.01) insulin secretion. It is concluded that the first phase response to a glucose pulse is independent of the steady-state pre-stimulus glucose concentration and is directly enhanced by tolbutamide; in contrast, second phase is related to both the steady-state pre-stimulus glucose level and tolbutamide. These findings suggest that changes in basal or pre-stimulus plasma glucose during therapy with sulphonylurea drugs may be expected to influence the second phase insulin responses to glucose challenge.

Glycemic control and nerve conduction abnormalities in non-insulin-dependent diabetic subjects.

The influence of therapy of hyperglycemia on the progression of diabetic neuropathy is unclear. We studied variables of glycemia and motor and sensory nerve conduction velocity in a group of 18 non-insulin-dependent diabetic subjects before and after institution of diabetes therapy. Diabetes therapy significantly reduced variables of glycemia after 1, 3, 6, and 12 months. Conduction velocity of the median motor nerve was improved from baseline at each time tested during treatment. In addition, peroneal and tibial motor nerve conduction velocities improved in patients whose levels of hyperglycemia were lowered. Moreover, extent of improvement of conduction velocity of some motor nerves was related to the degree of reduction of hyperglycemia. Sensory nerve conduction velocity was not altered by diabetes therapy. These findings support the hypothesis of a metabolic component to diabetic neuropathy and suggest that optimal glycemic control may be beneficial to patients with this disorder.

Diabetic neuropathy and plasma glucose control.

Diabetic neuropathy is defined, and theories of its pathogenesis are reviewed. Recent studies designed to investigate the influence of plasma glucose on nerve function in noninsulin-dependent diabetic patients are summarized. Motor nerve conduction velocities in the median and peroneal nerves were measured using a double-stimulus technique, and sensory conduction velocity was measured by conventional methods before and after therapy with oral agents or insulin. The degree of hyperglycemia was assessed by measurement of fasting plasma glucose and glycosylated hemoglobin concentrations. The degree of slowing in motor nerve conduction velocity in untreated patients was found to correlate with the fasting plasma glucose and glycosylated hemoglobin concentrations, but sensory nerve function, although abnormal, did not show such correlation. Reduction of hyperglycemia was associated with improvement in motor nerve conduction velocity in the peroneal and median motor nerves of these patients, but sensory nerve conduction velocity showed no such improvement. Improvement in median motor nerve conduction velocity was directly related to the degree of reduction in fasting plasma glucose concentration. These findings suggest that metabolic factors related to hyperglycemia are important in the impaired motor nerve function seen in noninsulin-dependent patients with maturity-onset diabetes.

Comparison of a colorimetric assay for glycosylated hemoglobin with ion-exchange chromatography.

Because levels of glycosylated hemoglobin (GHb) are increased in diabetes and reflect the previous metabolic control, clinicians and clinical investigators are finding increasing applications for measurements of GHb in diabetic patients. We report the characterization of a colorimetric assay procedure for GHb and compare its performance with that of a commonly used assay by ion-exchange chromatography. Although results of GHb determination by both methods correlate highly (r = 0.946, P less than 0.001), the two procedures estimate different glycosylated fractions. The colorimetric procedure is nonstoichiometric, requiring careful standardization of assay conditions, including the concentration of total hemoglobin in the assayed aliquot, to achieve precision and permit comparison of results. We characterized the effect of storage of hemolysates or packed erythrocytes on the subsequent determination of GHb by both methods. Determinations of GHb by the colorimetric method, but not by column chromatography, are reproducible on hemolysates or packed erythrocytes on the subsequent determination of GHb by both methods. Determinations of GHb by the colorimetric method, but not by column chromatography, are reproducible on hemolysates or packed erythrocytes stored frozen for at least 5 mo. A unique advantage of the colorimetric procedure is the capability to estimate GHb levels when variant hemoglobins, including fetal and sickle hemoglobins, are present.

Nerve conduction abnormalities in untreated maturity-onset diabetes: relation to levels of fasting plasma glucose and glycosylated hemoglobin.

The role of metabolic abnormalities in the development of diabetic neuropathy is controversial. To investigate the influence of hyperglycemia on nerve conduction, we studied 20 untreated maturity-onset diabetic patients and 23 normal control subjects of similar age. Nerve conduction velocity of motor (median, peroneal, and tibial) and sensory (median and sural) nerves in diabetic patients was significantly slowed and H-reflex latency time prolonged. Levels of fasting plasma glucose in diabetic subjects were correlated with slowed motor conduction velocity of the median, peroneal, and tibial nerves but not with sensory nerve conduction velocities. Levels of glycosylated hemoglobin, an index of long-term glycemia, were correlated with slowing of peroneal motor conduction velocity in diabetic patients. These associations could not be explained by patient age or duration of diabetes. These findings suggest that the degree of hyperglycemia of untreated maturity-onset diabetes contributes to the motor nerve conduction abnormalities in this disease.

Glycosylated hemoglobin in normal subjects and subjects with maturity-onset diabetes. Evidence for a saturable system in man.

Concentrations of glycosylated hemoglobin (GHb) are elevated in diabetes mellitus and are believed to reflect previous metabolic control. To better define possible determinants of GHb in man, we investigated the relationship between GHb and both fasting plasma glucose (FPG) and basal insulin (IRI) in 42 normal subjects and 29 patients with maturity-onset diabetes. Concentrations of GHb in diabetic subjects (12.7 +/- 3.4, x +/- S.D., per cent total hemoglobin) were significantly higher than in normal subjects (8.2 +/- 1.2, p less than 0.001). In normal subjects, FPG (r = 0.52) and GHb (r = 0.58) (both p less than 0.001) correlated with age. GHb did not correlate with IRI in either group. However, GHb was closely associated with FPG in both normal (r = 0.60, p less than 0.001) and diabetic (r = 0.85, p less than 0.001) subjects. Linear regression analysis of the data for the two groups combined was highly significant (r = 0.91, p less than 0.001). However, the slope of the regression line for GHb versus FPG seen in normal subjects was significantly steeper than that of diabetic patients (p less than 0.005). A curve describing a nonenzymatic saturable model was also found to fit the data of the two groups combined (r = 0.85, p less than 0.001), suggesting the possible existence of a saturable system for glycosylation in man.