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Biomedical subjects

M Schmolke

Publications and source records attributed to M Schmolke.

At least 19 recordsLinked to original sources

Molecular mapping of resistance genes to tan spot [Pyrenophora tritici-repentis race 1] in synthetic wheat lines.

Synthetic wheat lines (2n = 6x = 42, AABBDD), which are amphiploids developed from the hybrid between tetraploid wheat (Triticum turgidum L., 2n = 4x = 28, AABB) and Aegilops tauschii Coss. (2n = 2x = 14, DD), are important sources of resistance against tan spot of wheat caused by Pyrenophora tritici-repentis. In the present study, inheritance, allelism and genetic linkage analysis in synthetic wheat lines have been carried out. Segregation analysis of the phenotypic and molecular data in F(2:3) populations of CS/XX41, CS/XX45, and CS/XX110 has revealed a 1:2:1 segregation ratio indicating that resistance of tan spot in these synthetic lines is controlled by a single gene. Allelism tests detected no segregation for susceptibility among F(1) and F(2) plants derived from intercrosses of the resistance lines XX41, XX45 and XX110 indicating that the genes are either allelic or tightly linked. Linkage analysis using SSR markers showed that all the three genes: tsn3a in XX41, Tsn3b in XX45 and tsn3c in XX110 are clustered in the region around Xgwm2a, located on the short arm of chromosome 3D. The linked markers and genetic relationship of these genes will greatly facilitate their use in wheat breeding and deployment of cultivars resistant to tan spot.

Alleles↗

Molecular mapping of Fusarium head blight resistance in the winter wheat population Dream/Lynx.

Fusarium head blight (FHB), mainly caused by Fusarium graminearum and F. culmorum, can significantly reduce the grain quality of wheat (Triticum aestivum L.) due to mycotoxin contamination. The objective of this study was to identify quantitative trait loci (QTLs) for FHB resistance in a winter wheat population developed by crossing the resistant German cultivar Dream with the susceptible British cultivar Lynx. A total of 145 recombinant inbred lines (RILs) were evaluated following spray inoculation with a F. culmorum suspension in field trials in 2002 in four environments across Germany. Based on amplified fragment length polymorphism and simple sequence repeat marker data, a 1,734 cM linkage map was established assuming that the majority of the polymorphic parts of the genome were covered. The area under disease progress curve (AUDPC) was calculated based on the visually scored FHB symptoms. The population segregated quantitatively for FHB severity. Composite interval mapping analysis for means across the environments identified four FHB resistance QTLs on chromosomes 6AL, 1B, 2BL and 7BS. Individually the QTLs explained 19%, 12%, 11% and 21% of the phenotypic variance, respectively, and together accounted for 41%. The QTL alleles conferring resistance on 6AL, 2BL and 7BS originated from cv. Dream. The resistance QTL on chromosome 6AL partly overlapped with a QTL for plant height. The FHB resistance QTL on 7BS coincided with a QTL for heading date, but the additive effect on heading date was of minor importance. The resistance QTL on chromosome 1B was associated with the T1BL.1RS wheat-rye translocation of Lynx.

Area Under Curve↗

Influence of dehydration on glycerophosphorylcholine and choline distribution along the rat nephron.

Glycerophosphorylcholine is one of the four major organic osmolytes in renal medullary cells, changing their intracellular osmolyte concentration in parallel with extracellular tonicity during cellular osmoadaptation. In this study, the tubular content of glycerophosphorylcholine was quantified in untreated and 48-h-dehydrated male rats. A chemiluminescence ultra-micromethod was developed to measure choline at the picomolar level in single tubules microdissected from collagenase-treated kidneys. The glycerophosphorylcholine level was calculated as the difference between total choline after acid hydrolysis and the free tubular choline content. In accordance with the glycerophosphorylcholine distribution pattern in different renal zones of untreated rats, low amounts of glycerophosphorylcholine were found in all cortical and outer medullary structures (< 35 pmol/mm), whereas increasing amounts were detected towards the papillary tip (163 pmol/mm). As a percentage of total choline, the level of free tubular choline varied from 4.2% in outer medullary proximal tubules to 30.3% in the inner medullary collecting ducts adjacent to the outer medulla (IMCD1). Antidiuresis led to a nearly twofold increase in glycerophosphorylcholine content in papillary collecting ducts. The osmolality-dependent regulation of organic osmolytes in single microdissected tubules has been demonstrated for the first time. Furthermore, the high tubular glycerophosphorylcholine concentration compared to sorbitol and myo-inositol emphasizes the predominance of glycerophosphorylcholine in the inner medulla and papilla of the rat kidney.

Animals↗

Cerebrospinal beta-amyloid ((1-42)) in early Alzheimer's disease: association with apolipoprotein E genotype and cognitive decline.

The concentration of beta-Amyloid ((1-42)) protein (Abeta42) in cerebrospinal fluid (CSF) was determined in 75 Alzheimer's disease (AD) patients, 35 patients with other causes of dementia and 30 cognitively healthy age-matched controls. A significant decrease of Abeta42 concentration was found in AD patients, even in 25 subjects with very mild dementia as compared to patients with other causes of dementia and controls. Within AD patients we observed a significant decline of Abeta42 from very mild to mild and moderate dementia. In addition, Abeta42 levels were negatively correlated with the severity of cognitive impairment and with the number of varepsilon4 alleles inherited. We conclude that measurement of Abeta42 in CSF might be helpful for identifying AD at an early stage and also for tracking the clinical course.

Age Factors↗

[Tau protein. A potential biological indicator for early detection of Alzheimer disease].

In 40 patients with Alzheimer's disease (AD), in 5 patients with non-AD dementia and in 36 cognitively normal controls the concentration of protein tau was determined in the cerebrospinal fluid (CSF). Of the AD patients, 19 were very mildly demented (MMSE score from 25 to 28). Even in these patients, CSF tau was significantly more elevated than in controls. In the non-AD patients protein tau was less increased. Among the AD patients there was no association between CSF tau and severity of cognitive impairment or deficit in cerebral blood flow, determined by SPECT. Our findings suggest that CSF tau may be elevated even at the predementia stage of AD and be useful as a biological marker for the early recognition of the disease.

Adult↗

[MDMA ("Ecstasy") use--an overview of psychiatric and medical sequelae].

Epidemiological research and Substance Abuse Warning Systems point to a sharp increase in the use of "Ecstasy" (MDMA), as well as to structural changes in the drug scene in and outside Europe. For some consumers, "Ecstasy" opens the door to the abuse of other illegal substances. Since the mid-eighties psychiatric complications and consequences of the abuse of MDMA have been reported in at least 48 cases. It is necessary to differentiate between acute psychiatric complications, which subside completely when the level of intoxication comes down, toxic psychoses and long-term psychiatric diseases as a consequence of substance abuse. The latter involve atypical and paranoid psychoses, depressions, panic disorders, depersonalisation and behavioural disorders. Convulsive seizures are among the most common problems involving the central nervous system. Furthermore, there have been reports on cerebrovascular accidents and intracranial haemorrhages. Literature reports on at least 53 cases of medical complications in abusers of MDMA, 14 of which came to a lethal end. Research still blatantly lacks prospective epidemiological and clinical studies on a sufficiently large scale to identify different developments of dependency and predictors of harmful and unhealthy consumption.

Brain↗

Cerebrospinal protein tau is elevated in early Alzheimer's disease.

Protein tau concentration was determined by an enzyme linked immunoassay (ELISA) in cerebrospinal fluid (CSF) of 22 patients with clinically diagnosed Alzheimer's disease (AD), in three patients with dementia caused by other neurological disorders (OND) and in 19 cognitively healthy controls. A significantly elevated protein tau concentration was found in AD patients as compared with controls, even in 11 patients with very mild dementia. There was no correlation between protein tau and the severity of cognitive impairment as assessed with the Mini Mental State Examination (MMSE). Tau concentrations were not or only slightly elevated in OND. We conclude that protein tau in CSF might be helpful as a biological marker for the early diagnosis of AD.

Aged↗

Site-specific regulation of organic osmolytes along the rat nephron.

The regulation of organic osmolytes was investigated in acute furosemide and chronic lithium diuresis along the nephron and in urinary bladder of rats. Sorbitol, myo-inositol, glycerophosphorylcholine, and betaine were measured enzymatically or by high performance liquid chromatography in homogenates and bioluminometrically in microdissected tubules. In untreated rats, all osmolytes except myo-inositol increased along the corticopapillary axis. An efflux of all osmolytes (-50%) was observed in homogenates of outer and inner medulla after acute furosemide diuresis (15 min, urinary osmolality = 329 mosmol/kgH2O) and for both polyols in microdissected tubules (30 min). In urinary bladder, only low concentrations of myo-inositol were found not to be affected by furosemide treatment. Chronic lithium treatment (7 days; urinary osmolality = 385 mosmol/kgH2O) decreased inner medullary but not outer medullary osmolyte concentrations. The results confirm a site-specific organic osmolyte pattern along the rat nephron, which is rapidly changed in a segment-specific way by different mechanisms of diuresis. The bladder epithelium does not accumulate organic osmolytes because no "osmotic gap" exists across the basolateral membrane. The osmotic difference across the apical membrane is maintained by the apical tightness of these cells.

Animals↗

Determination of choline dehydrogenase activity along the rat nephron.

A radioenzymatic microassay was developed to quantitate choline dehydrogenase activity in single microdissected nephron segments. This enzyme is the rate limiting step in the biosynthesis of betaine, which serves as an intracellular osmoregulatory organic solute in mammalian kidney. The enzyme localized in renal mitochondrial inner membrane forms betaine aldehyde, which in the assay is converted to betaine by oxidative treatment. A histochemical procedure based on the formazan detection of tetranitroblue tetrazolium chloride was applied in parallel. The results show that activities in proximal convoluted and straight tubules are more than 5 times higher (21 to 25 pmol h-1 mm tubule-1) compared to distal nephron segments with no significant differences along the proximal tubule. Along the osmotic gradient from the outer medullary towards the papillary structures enzyme activities increased in ascending limbs of Henle's loop and collecting tubules. Collecting ducts showed two times higher activities than ascending loop segments when corrected for tubular cell volumes. The quantitative data were confirmed by the histochemical procedure. The results allow for the conclusion that betaine synthesis is sufficient to build up renal betaine, but cannot explain the distribution pattern of betaine along the corticopapillary axis. Additional mechanisms like intrarenal and tubular transport have to be postulated.

Alcohol Oxidoreductases↗

Intrarenal distribution of organic osmolytes in human kidney.

The distribution pattern of renal organic osmolytes in surgically explanted human kidneys was investigated and compared with that of untreated Sprague-Dawley rats (Uosmo = 1186 mosmol/kg H2O). Sorbitol, myo-inositol, glycerophosphorylcholine and betaine were measured by liquid chromatography (HPLC) in homogenates of five different kidney zones from the cortex towards the papillary tip. All four organic osmolytes were detected as in human as in rat kidney. The expected increase from the inner medulla to the papillary tip for sorbitol and betaine, and from the outer medulla to the papilla for glycerophosphorylcholine, was observed in rats, but not in explanted human kidney. An inverse distribution pattern was observed with decreasing tissue contents from the inner and outer medulla to the papillary tip for all organic osmolytes and urea. This intrarenal osmolyte profile is in accordance with that observed during water and lithium diuresis in rats. Therefore it can be assumed that a loss of renal medullary osmolytes during the intra-operative treatment of patients led to the observed osmolyte pattern. We conclude that organic osmolytes are involved in renal medullary osmoadaptation of humans.

Animals↗

Osmolytes.

The cells of the renal medulla osmotically adapt to chronic alterations in extracellular tonicity by appropriate changes in the intracellular contents of organic osmoeffectors. The major organic osmolytes are glycerophosphorylcholine, betaine, myo-inositol, sorbitol, and, possibly, taurine. When the concentrations of poorly permeant external solutes are acutely reduced, cells that have been adapted to high tonicities rapidly release organic osmolytes via specific transmembrane transport pathways. In contrast, when medullary cells are depleted of organic osmolytes, osmolyte accumulation on acute elevation of external tonicity is slow and involves stimulation of uptake, intracellular de novo synthesis, or inhibition of intracellular degradation, and is preceded by increased intracellular electrolyte concentrations. The available evidence suggests that this rise in intracellular ionic strength plays an important role in the initiation of those processes responsible for full adaptation of renal medullary cells to high tonicities. Recently, complementary DNAs encoding a myo-inositol and a betaine transporter have been isolated.

Animals↗

Osmolytes in renal medulla during rapid changes in papillary tonicity.

The effect of acute changes in extracellular tonicity on cell electrolyte concentrations at the renal papillary tip and on organic osmolytes in different kidney zones was studied using electron microprobe analysis and high-performance liquid chromatography in four groups of rats: controls, 1- or 4-h water diuresis, and 4-h water diuresis followed by 30-min deamino-[Cys1,D-Arg8]vasopressin (ddAVP). The sum of the papillary interstitial concentrations of Na, K, and Cl was reduced from 981 mmol/kg wet wt in controls to 318 mmol/kg wet wt after 4-h diuresis and increased after ddAVP to 840 mmol/kg wet wt. In papillary collecting ducts intracellular electrolytes fell from 225 to 156 mmol/kg wet wt after 4-h diuresis and rose to 268 mmol/kg wet wt (significantly higher than control) after ddAVP. Organic osmolytes [sum of glycerophosphorylcholine (GPC), betaine, myo-inositol, and sorbitol] at the papillary tip decreased from 2,018 (control) to 1,037 mmol/kg protein after 4-h diuresis and did not increase after ddAVP. After ddAVP, cell P concentration, an index of cell GPC concentration, increased, indicating cell shrinkage. GPC concentration increased, indicating cell shrinkage. The results suggest that the concentrations of all osmoeffectors in papillary cells initially increase due to cell shrinkage in response to hypertonic stress. The higher intracellular ionic strength may be a signal for modulation of transport and metabolism of organic osmolytes.

Animals↗

Renal sorbitol, myo-inositol and glycerophosphorylcholine in streptozotocin-diabetic rats.

The polyols, sorbitol and myo-inositol, seem to be involved in the development of diabetic complications of different organs. High concentrations of both polyols were found in kidney medulla in addition to trimethylamines. To investigate the influence of diabetes mellitus on the regulation of both polyols and glycerophosphorylcholine in kidney, these osmolytes were quantitated enzymatically along the corticopapillary axis in untreated, streptozotocin-diabetic and insulin-treated streptozotocin-diabetic rats. In control animals three individual osmolyte patterns were found: a steep gradient of sorbitol in the papilla, increasing amounts of glycerophosphorylcholine from the outer medulla to the papilla, and nearly equal amounts of myo-inositol in the renal medulla, decreasing towards the cortex. Diabetic rats exhibit an up to fourfold increase of inner medullary sorbitol, whereas myo-inositol was only elevated in the outer medulla. Glycerophosphorylcholine was lowered in the papillary tip and elevated in the outer medulla and cortex. Insulin treatment reduced sorbitol to a concentration between those of diabetic and control rats, caused a restoration of glycerophosphorylcholine in the papillary tip and outer medulla to control values, and increased cortical myo-inositol. These data confirm previous in vitro data, which show that papillary sorbitol specifically increases in hyperglycaemic states, thereby counteracting the increased extracellular tonicity due to elevated tissue glucose concentrations. Imbalance of extra- vs intracellular osmolality during insulin treatment may be involved in the pathomechanism of renal papillary necrosis.

Animals↗