Stabilizing feedbacks in glacier-bed erosion.

Glaciers often erode, transport and deposit sediment much more rapidly than nonglacial environments, with implications for the evolution of glaciated mountain belts and their associated sedimentary basins. But modelling such glacial processes is difficult, partly because stabilizing feedbacks similar to those operating in rivers have not been identified for glacial landscapes. Here we combine new and existing data of glacier morphology and the processes governing glacier evolution from diverse settings to reveal such stabilizing feedbacks. We find that the long profiles of beds of highly erosive glaciers tend towards steady-state angles opposed to and slightly more than 50 per cent steeper than the overlying ice-air surface slopes, and that additional subglacial deepening must be enabled by non-glacial processes. Climatic or glaciological perturbations of the ice-air surface slope can have large transient effects on glaciofluvial sediment flux and apparent glacial erosion rate.

Splenic trauma: value of follow-up CT.

PURPOSE: To determine the value of follow-up computed tomography (CT) after expectant treatment in patients with clinically stable blunt splenic trauma. MATERIALS AND METHODS: Medical records and CT studies for 42 patients were reviewed, and injuries were graded on a scale of 1-6. Patients were divided into three groups: stable patients with no follow-up CT (group 1, n = 14), stable patients with follow-up CT (group 2, n = 22), and symptomatic patients with follow-up (group 3, n = 6). Serial hemoglobin values and clinical findings at follow-up CT were reviewed. RESULTS: All patients in groups 1 and 2 remained clinically stable with good outcomes. In group 3, follow-up CT scans demonstrated worsening condition in four patients (67%), and three of the four had poor outcomes. CONCLUSION: Follow-up CT may be unnecessary in patients with clinically stable splenic trauma.

Calbindin D28K expression in transfected mouse NIH3T3 cells.

Calbindin D28K (formerly known as vitamin D-dependent calcium binding protein and referred to here as calbindin) is found in a wide variety of tissues, but only in certain cells within those tissues. Apart from its ability to bind calcium, nothing is known about its function in these cells. To investigate its role we have transfected the chick calbindin cDNA into mouse NIH3T3 fibroblasts and established a new cell line where calbindin is permanently expressed. Immunofluorescence studies show that calbindin is distributed throughout the cytoplasm, and treatment of the cells with cycloheximide shows that it has a relatively long half-life within the cell. Measurements of intracellular calcium concentration using Fura-2 suggest that the presence of calbindin within the cells does not affect the increase in intracellular calcium levels which occurs in response to serum stimulation or the rate at which these return to the basal level, but that it may act as a buffer for the entry of extracellular calcium.

Time dependency of 1,25(OH)2D3 induction of calbindin mRNA and calbindin expression in chick enterocytes during their differentiation along the crypt-villus axis.

Quantitative methods of in situ hybridization and immunocytochemistry have been used to measure 1,25 dihydroxyvitamin D3 (1,25(OH)2D3) induction of calbindin mRNA and calbindin protein expressed in jejunal enterocytes at all points along the crypt-villus axis over a 24 h period. Small amounts of calbindin mRNA detected in vitamin D3 deficient (D-deficient) chick intestine increased rapidly to maximal values 8 h after hormone injection. The magnitude of this response was inversely related to age of enterocyte measured separately by injecting tritiated thymidine into D-deficient and 1,25(OH)2D3-injected birds. Enterocytes of all ages expressed small amounts of calbindin 3 h after hormone injection. This amount of calbindin then increased up to 24 h after hormone injection. Maximal calbindin expression took place in basal villus enterocytes. Later decrease in the ability of upper villus enterocytes to express calbindin was associated with a similar fall in calbindin mRNA expression. Previously it was suggested that inefficient translation to calbindin mRNA might take place in basal villus enterocytes 48 h after vitamin D injection. Present work using 1,25 (OH)2D3 shows that calbindin expression takes place at a constant rate during this early stage of enterocyte development. Secondary events limiting higher rates of calbindin synthesis in upper crypt and basal villus enterocytes remain to be identified.

Estrogen and a calcium flux dependent factor modulate the calbindin gene expression in the uterus of laying hens.

The dependency of calbindin 28K synthesis on estrogen and vitamin D and its relationship with calcium transfer were investigated in the uterus of laying hens by dot blot hybridization analysis using as a probe a cDNA coding for calbindin. Estrogen stimulated growth of the oviduct and uterine calbindin synthesis in juvenile D-deficient female chicks. In laying hens, calbindin mRNA increased most markedly during shell deposition but calbindin concentrations did not fluctuate during the ovulatory cycle. Suppression of shell formation within a few hours reduced calbindin mRNA levels and lowered uterine calbindin concentrations when egg expulsions were continued for several days. The concentration of calbindin and its mRNA increased when shell formation resumed in hens previously laying shell-less eggs. These increases were maintained in hens parathyroidectomized just before shell resumption. Lowering dietary calcium decreased uterine calcium transfer and calbindin concentration but its mRNA level was unaffected. It is suggested that uterine calbindin synthesis is regulated in a tissue-specific manner through transcriptional mechanisms irrespective of change in vitamin D; calbindin synthesis is stimulated by estrogens as part of its effect on oviductal growth but its regulation predominantly involves a calcium flux dependent factor associated with shell calcification.

Regulation of calbindin D 28K and its mRNA in the intestine of the domestic hen.

Intestinal calbindin synthesis in laying hens was analyzed to assess controlling factors operating during egg formation. In the absence of vitamin D, calbindin was not induced by estrogen and testosterone. In immature vitamin D-replete pullet, blood levels of 1,25(OH)2D3 increased in response to estrogen but the duodenal concentration of calbindin and its mRNA were increased only when testosterone was given together with estrogen. The plasma concentration of 1,25(OH)2D3 and the duodenal levels of calbindin and its mRNA were substantially higher in laying hens than in immature pullets. No differences in these parameters were observed between the stages of the ovulatory cycle. Suppression of shell formation for a week decreased the concentration of 1,25(OH)2D3 and of duodenal calbindin but did not affect the level of its mRNA. When egg shell formation resumed in hens previously laying shell-less eggs, the concentrations of 1,25(OH)2D3 and of calbindin and its mRNA increased toward the end of shell formation. A most important factor regulating intestinal calbindin synthesis in laying hens turned out to be 1,25(OH)2D3. Intestinal calbindin mRNA is more stable in laying hens than in young birds as its concentration declines more slowly when the stimulation provided by 1,25(OH)2D3 is withdrawn, as occurs following suppression of shell formation and after parathyroidectomy in laying birds. Intestinal calbindin mRNA is therefore increased by a process other than increasing 1,25(OH)2D3 formation. The factor influencing the stability of this mRNA in laying hens could be calcium. It is concluded that in hens the increased duodenal calbindin synthesis elicited by plasma 1,25(OH)2D3 at sexual maturity primarily involves a transcriptional process and the stabilization of the mRNA.(ABSTRACT TRUNCATED AT 250 WORDS)

Cerebral cortical calbindin D28K and parvalbumin neurones in Down's syndrome.

Anti-calbindin D28K (CaBP) and anti-parvalbumin (PVA) antibodies were used to study the number and size of neurones containing these two calcium binding proteins in post-mortem brains from 7 neurologically normal controls and from 4 elderly patients with clinically diagnosed Down's syndrome (DS) and whose brains contained numerous senile plaques and neurofibrillary tangles. The possible co-existence of these two calcium binding proteins in human cerebral cortex was also examined. In the controls, CaBP immunoreactive neurones were mainly non-pyramidal neurones although some pyramidal neurones were also CaBP immunoreactive. All the PVA immunoreactive neurones were non-pyramidal cells. CaBP and PVA did not apparently co-exist with each other in cortical neurones. When compared with the neurologically normal controls, the number and size of CaBP and PVA immunoreactive neurones were significantly reduced in the cortex of patients with DS. These findings show that CaBP and PVA containing cortical neurones are affected in elderly persons with DS.

Differential regulation of calbindin-D28K mRNA in the intestine and eggshell gland of the laying hen.

The effect of shell calcification and 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) on calbindin-D28K (previously known as vitamin D-dependent calcium-binding protein) and calbindin mRNA was investigated in the intestine and eggshell gland (ESG) of juvenile female chicks, laying hens and non-laying female birds with active gonads. Increasing amounts of 1,25-(OH)2D3 were fed to laying hens and juvenile birds treated with oestradiol to develop the ESG. The intestinal concentration of calbindin was increased 30-fold by 1,25-(OH)2D3 in chicks treated with oestradiol and fed a vitamin D-deficient diet. In these same animals, 1,25-(OH)2D3 had no effect on the formation of calbindin mRNA or calbindin in the ESG even though fully viable 1,25-(OH)2D3 receptors are present in this tissue. In laying birds fed adequate amounts of vitamin D3, intestinal, but not ESG, calbindin was increased by the addition of 1,25-(OH)2D3 to the diet. At the onset of egg production the concentrations of calbindin and calbindin mRNA were increased in the intestine and ESG. This increase occurred within the period of calcification of the first egg, through a process unaffected by vitamin D. Calcification of the first egg increased the concentration of calbindin in the ESG by eight- to tenfold, although the concentration of calbindin mRNA was increased by only two- to threefold. These results suggest that the induction of calbindin synthesis by 1,25-(OH)2D3 or by the egg calcification process is associated with an increase in the concentration of calbindin mRNA in the ESG and intestine.(ABSTRACT TRUNCATED AT 250 WORDS)

The use of quantitative immunocytochemistry (QICC) to measure calbindin D28k-like immunoreactivity in the rat brain.

We have developed a method of quantitative immunocytochemistry using an iodinated second antibody to visualise the anatomical distribution of primary antibodies in tissue sections, by macroautoradiography. Computer-assisted densitometry was used to analyse the pattern of optical densities within autoradiograms. The amount of antigen present in tissue sections was then quantified by comparison with non-biological standards which were processed in parallel with the tissue sections. Using this technique we have measured calbindin like-immunoreactivity in 4 areas of rat brain and have found that the values obtained are similar to those obtained by radioimmunoassay. A similar approach can be used to quantify autoradiograms by comparison with antigen standards to measure amounts of radiolabelled immunoreactivity and determine concentrations of biologically active molecules in discrete brain areas.

Increases in calbindin D 28K mRNA in the uterus of the domestic fowl induced by sexual maturity and shell formation.

Uterine concentrations of calbindin D 28K mRNA were measured in immature pullets and laying hens by dot-blot hybridization using a [32P]cRNA probe prepared from the calbindin cDNA. In immature pullets, estrogen increased the calbindin mRNA level and the plasma concentration of 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3]. When testosterone was administered with estrogen there was a further increase in calbindin and its mRNA and an increase in the free 1,25-(OH)2D3 index calculated as the ratio of the molar concentrations of total 1,25-(OH)2D3 and vitamin D-binding protein (DBP). In laying hens the uterine concentration of calbindin mRNA was low 4 hr after ovulation, but increased most markedly 12 and 18 hr later, when shell calcification took place. Calbindin concentration remained unchanged during the different stages of egg formation but was much higher in laying hens than in pullets treated with sex steroids. Suppression of shell formation by premature expulsion of the egg decreased the concentrations of calbindin mRNA and uterine calbindin and the free 1,25-(OH)2D3 index in the plasma. A concomitant increase in calbindin and its mRNA was observed at resumption of shell formation in hens previously laying shell-less eggs. Withdrawal of food for 44 hr decreased the uterine concentration of calbindin and its mRNA without a change in the free 1,25-(OH)2D3 index in the blood. It is concluded that the synthesis of uterine calbindin is stimulated primarily at sexual maturity and at calcification of the first shell by transcriptional processes. The daily increase in calbindin mRNA associated with shell formation and the absence of a concomitant change in calbindin concentration suggest that post-transcriptional processes exist and that stimuli other than the sex steroid or the 1,25-(OH)2D3 are involved in regulation of calbindin synthesis in the uterus.

Presence of calbindin-D 28K in endocrine pancreatic tumoral cells of the RINm5F line.

Calbindin-D 28K expression in insulin-producing tumoral cells of the RINm5F line was assessed by Western-blot and high pressure liquid chromatography. Western blot analysis demonstrated the presence in RINm5F cell homogenates of a protein recognized by a specific polyclonal antibody against chick calbindin. Proteins with apparent molecular weights (mol wt) of 44, 47, 56, and 85 kD were also recognized by the antiserum in RINm5F cell extract, but not in normal rat islet extract. HPLC heat-resistant protein extract from RINm5F cell homogenates revealed three calbindin positive peaks: a major peak with a retention time (20.5 min) identical to that found in a rat cerebellar extract and two minor peaks with shorter retention times. The calbindin content of RINm5F cells was apparently unaffected after 9 d culture in a medium supplemented with 10% calf serum pretreated with dextran-charcoal to remove 1,25-dihydroxyvitamin D3.

Calbindin-immunoreactive cholinergic neurones in the nucleus basalis of Meynert in Alzheimer-type dementia.

An antibody to the calcium binding protein, calbindin D28K (CaBP), was used to study the number and size of CaBP-immunoreactive neurones in the nucleus basalis of Meynert (nbM) of postmortem human brains from neurologically normal controls and from patients with neuropathologically diagnosed Alzheimer-type dementia (ATD). In controls, almost all the large neurones and their processes in the nbM were CaBP immunoreactive. Compared to neurologically normal controls the number of CaBP-immunoreactive neurones in the nbM in patients dying with ATD was significantly reduced and there was a clear loss of the majority of CaBP immunoreactive neurones. The few remaining nbM CaBP immunoreactive neurones in the ATD cases were smaller than those in the neurologically normal controls. Double-staining experiments revealed that many of the nbM CaBP-immunoreactive neurones contained choline acetyltransferase immunoreactivity, so that CaBP is an alternative marker for the nbM cholinergic neurones in the human fore-brain. These findings suggest that a disturbance in calcium homeostasis may be a possible factor contributing to the loss of these cholinergic/CaBP-containing neurones.

The human calbindin 27-kDa gene: structural organization of the 5' and 3' regions, chromosomal assignment, and restriction fragment length polymorphism.

The 5' and 3' regions of the human gene coding for calbindin 27 kDa were cloned and sequenced. Structural features of the 5' region included the presence of an Alu repeat and two elements regularly associated with eukaryotic promoters: an alternating purine-pyrimidine element and a homopurine-homopyrimidine box. The 3' region contained a second Alu family member and a degenerate 1.4-kb L1 repeat. A comparison with the chicken promoter was made in order to define regions conserved in evolution and potentially important in gene expression regulation. The greater similarity is located around the TATA box, but strongly conserved elements were not found. The gene was assigned to chromosome 8 by using human-rodent hybrid cell lines. Two restriction fragment length polymorphisms (HindIII and SacI) were detected with a cDNA probe recognizing the 3' end of the gene.

Calbindin 28 kDa in endocrine cells of known or putative calcium-regulating function. Thyro-parathyroid C cells, gastric ECL cells, intestinal secretin and enteroglucagon cells, pancreatic glucagon, insulin and PP cells, adrenal medullary NA cells and some pituitary (TSH?) cells.

The distribution of calbindin in some endocrine glands (thyroid, parathyroid, ultimobranchial body, pituitary and adrenals) and in the diffuse endocrine cells of the gut and pancreas has been investigated immunohistochemically using an antiserum raised against the 28 kDa calbindin from chicken duodenum. The identity of calbindin-immunoreactive cells in a number of avian and mammalian species was ascertained by comparison with hormone-reactive cells in consecutive sections or by double immunostaining of the same section with both calbindin and hormone antibodies. Calcitonin-producing C cells of the mammalian and avian thyroid, parathyroid or ultimobranchial body, PP, glucagon and insulin cells of the mammalian and avian pancreas, enteroglucagon cells of the avian intestine, secretin cells of the mammalian duodenum, histamine-producing ECL cells of the mammalian stomach, as well as noradrenaline-producing cells of the adrenal medulla and some (TSH?) cells of the adenohypophysis were among the calbindin-immunoreactive cells. Although some species variability has been observed in the intensity and distribution of the immunoreactivity, especially in the pancreas and the gut, a role for calbindin in the mechanisms of calcium-mediated endocrine cell stimulation or of intracellular and extracellular calcium homeostasis is suggested.

Calbindin immunoreactivity is a characteristic of enterochromaffin-like cells (ECL cells) of the human stomach.

Immunoreactivity for the calcium binding protein, calbindin D28k has been localized in enterochromaffin-like (ECL) cells of the human stomach. The reactivity was observed with three different antisera, raised against bovine brain, primate brain, and chicken intestinal calbindin. The ECL cells were closed endocrine cells located at the bases of the oxyntic glands. They were not found in other regions of the stomach. No other gastric endocrine cells were reactive with these antisera.

Two classes of cortical GABA neurons defined by differential calcium binding protein immunoreactivities.

Calcium ions play a key role in many aspects of neuronal behavior and certain calcium binding proteins that may influence this behavior are differentially distributed in the central nervous system. In this study it is shown that immunoreactivity for calbindin-28 and for parvalbumin is localized in separate populations of inhibitory GABA interneurons in all areas of the neocortex of Old World monkeys. Virtually all GABA neurons show immunoreactivity for one or other calcium binding protein but, except for a few cells in layer IV, GABA cells do not show immunoreactivity for both proteins. Among the two cell populations, parvalbumin immunoreactivity characterizes basket neurons while calbindin immunoreactivity characterizes double bouquet neurons. These findings suggest that the two GABA cell types differ in their regulation of calcium homeostasis and may yield clues to their different roles in intracortical circuitry.

Loss of calbindin-28K immunoreactive neurones from the cortex in Alzheimer-type dementia.

An antibody raised against chick intestinal calbindin D28K was used to study the number and size of calbindin immunoreactive neurones in postmortem human brains from neurologically normal controls and from patients with neuropathologically diagnosed Alzheimer-type dementia (ATD). In the controls, calbindin immunoreactive neurones were observed in all cerebral cortex areas examined including the frontal, temporal and parietal cortices. When compared with the controls, the number and size of calbindin immunoreactive neurones were significantly reduced in the cortices of patients with ATD. These findings suggest that calbindin containing neurones are affected in ATD.