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Biomedical subjects

V Grill

Publications and source records attributed to V Grill.

At least 109 records · Page 6Linked to original sources
PubMed1994

Long-term elevation of 1,25-dihydroxyvitamin D after short-term intravenous administration of pamidronate (aminohydroxypropylidene bisphosphonate, APD) in Paget's disease of bone.

We report the prolonged biochemical changes that occurred in patients with Paget's disease when treated for 2-10 days with pamidronate disodium (3-amino-1-hydroxypropylidine-1,1-bisphosphonate, APD), by i.v. administration and observed for 6 months following therapy. In all 24 patients studied, bone resorption (measured by urinary hydroxyproline/creatinine ratio, OHP/Cr) fell sharply on treatment, from 0.12 +/- 0.02 (mean +/- SEM; above reference limits) to 0.04 +/- 0.008 (reference range 0.006-0.027 for females, 0.005-0.020 for males), remaining at this level for 6 months after therapy. A fall in serum ionized calcium (Ca2+) to just below the reference limits with treatment (1.11 +/- 0.02 mM; reference range 1.14-1.18 mM), followed by a rapid return to normal levels (1.14 +/- 0.02 mM, mean +/- SEM) within 8 days of treatment, was presumably due to the cessation of release of calcium from bone. This was followed by secondary hyperparathyroidism and a rise in serum 1,25-dihydroxyvitamin D [1,25(OH)2D]. The hormonal responses, however, were profound. Serum immunoreactive PTH (iPTH) rose to twice pretreatment values (86 +/- 11 pM, mean +/- SEM; reference range for iPTH, > 50 years, < 50 pM; < 50 years, < 40 pM), returning to normal 4-8 weeks after therapy. Serum 1,25-(OH)2D levels rose to three times pretreatment values (300 +/- 20 pM, mean +/- SEM; reference range 50-150 pM), remaining above reference limits 4-8 weeks after therapy (188 +/- 15 pM, mean +/- SEM) and returning to normal values only after 12 weeks.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

An immunohistochemical study of protein kinase C distribution in fetal mouse vertebral column.

Using polyclonal antibodies we have studied the distribution of protein kinase C in fetal mouse low thoracic vertebrae. By means of a pan protein kinase C antiserum recognizing the catalytic domain of the enzyme, we show that protein kinase C is markedly expressed in chondrocytes before birth. The enzyme seems to be very abundant in the more mature cells that are close to ossification centres as well as the periphery of the intervertebral disc, although it can also be detected in chondrocytes. In order to establish which protein kinase C isoenzyme(s) the chondrocytes produce, we employed polyclonal isoenzyme-specific antisera developed against three calcium-dependent isoforms (alpha, beta, gamma) and three calcium-independent isoforms (delta, epsilon, zeta). Secondary antibody conjugated to alkaline phosphatase revealed that chondrocytes markedly express the beta-isoform. Cells were also weakly stained by the anti-epsilon serum. The immunostaining was completely abolished by pre-incubating primary antibodies with the peptide antigens to which they were raised. These results suggest that protein kinase C (and particularly the beta isoform) could play an important role in mouse fetal chondrogenesis of the vertebral column.

Alkaline Phosphatase↗
PubMed1994

The growth of long bones in human embryological and fetal upper limbs and its relationship to other developmental patterns.

Measurements were made of the long bones of the upper limbs (humerus, ulna, radius) of 58 aborted embryos and fetuses, developmental age from 8 to 14 weeks, crown-rump length (CRL) between 38 and 116 mm. The specimens were cleared and double-stained, using alcian blue and alizarin red S for a differential detection of cartilage and bone. The values of both the total length (TL) and the ossified part (OL) of each long bone were related to the fetal developmental age previously estimated by freshly measured CRL. The relationship to another developmental pattern, i.e. the number of ossified centres in the vertebral column, suggested that the OL values could be much more significant than TL for the assessment of fetal growth.

Embryo, Mammalian↗
PubMed1994

Irreversible loss of normal beta-cell regulation by glucose in neonatally streptozotocin diabetic rats.

Animals with NIDDM display abnormal glucose regulation of insulin secretion and biosynthesis. We tested reversibility of abnormal regulation by normoglycaemia using an islet transplantation technique. Inbred non-diabetic and neonatally STZ diabetic rats (n-STZ) were used. Transplantations insufficient to normalize the blood glucose levels (200 islets under kidney capsule) were performed from diabetic to normal (D-N) and from diabetic to diabetic (D-D), as well as from normal to normal (N-N) and from normal to diabetic (N-D) rats. Four weeks after transplantation, graft bearing kidneys were isolated and perfused with Krebs-Henseleit bicarbonate buffer to measure insulin secretion in response to 27.8 mmol/l glucose and 10 mmol/l arginine. Four weeks of normoglycaemia failed to restore glucose-induced insulin secretion from n-STZ islets (glucose induced increment: -1.7 +/- 2.5 fmol/min in D-N, 1.2 +/- 7.1 fmol/min in D-D). In contrast to normal islets, normoglycaemia reduced insulin mRNA contents (60 +/- 24 in D-N, 496 +/- 119 in D-D; O.D.-arbitrary units). However, arginine-induced secretion was markedly enhanced by diabetic environment in both normal and n-STZ islet grafts. These results indicate that selected aspects of glucose recognition are irreversibly damaged by a long-term diabetic state or, alternatively, by a lasting effect of STZ administration.

Animals↗
PubMed1994

On the presence of a secondary cartilage in the mental symphyseal region of human embryos and fetuses.

The presence of a secondary cartilage in the mental symphyseal region was examined in this study. A double-staining method with alcian blue and alizarin red S was performed on both whole human embryos and fetuses (developmental age between 8 and 17 weeks, crown-rump length, CRL, between 37 and 124 mm) and their disjointed mandibles. Histological and histochemical techniques were applied to transverse serial sections of whole disjointed fetal heads. The ossification process observed in the mental symphysis is quite different from that of the mandibular body, whose membranous ossification is induced by the contiguous Meckel's cartilage. No evidence of any fusion of Meckel's cartilage with the symphyseal cartilage, that lies within the symphyseal space, was detected. On the basis of these findings, we suggested that the mental secondary cartilage is able to change into bone according to an endochondral ossification process. Moreover, the role of mechanical causes in the development of the mental symphysis was hypothesized.

Cadaver↗
PubMed1994

A quantitative study on the spatial and temporal ossification patterns of vertebral centra and neural arches and their relationship to the fetal age.

A double-staining technique on 37 human embryos and fetuses (crown-rump length, CRL, between 38 and 116 mm) has been performed to study the ossification patterns of the vertebral column. Different growth sequences for centra and neural arches were observed. The survey of ossified centers suggested it was possible to relate significantly their appearance with the CRL. On the basis of already known data defining the developmental age in relationship to the latter parameter, we suggest their numerical evaluation as a further parameter for the assessment of the fetal age. Therefore, we have worked out a table that may be used either to determine the normal fetal growth, or when other parameters cannot be relied upon (i.e. in morphological diseases) for this aim.

Cervical Vertebrae↗
PubMed1994

Relationships between diabetes duration, metabolic control and beta-cell function in a representative population of type 2 diabetic patients in Sweden.

To clarify whether metabolic control and beta-cell function deteriorate with increasing duration of diabetes, we investigated in a cross-sectional study Type 2 diabetic patients in an area-based population. Type 2 diabetic patients (n = 231: 112 males, 119 females) were identified by age at onset > or = 35 years, fasting levels of C-peptide > 0.04 nmol l-1, and absence of islet cell antibodies. Body weight was slightly elevated (BMI 26.8 +/- 0.3 kg m-2), however 76/210 (36%), had normal weight (BMI < 25 kg m-2). Fasting blood glucose rose significantly during the first 10 years of known diabetes from 8.2 +/- 0.3 mmol l-1 in patients with 0-5 years of duration to 9.9 +/- 0.7 mmol l-1 in those with 5-10 years of duration, p < 0.01 and HbA1c from 6.4 +/- 0.2 to 7.4 +/- 0.4%, p < 0.05. Fasting C-peptide levels decreased after 10 years duration from 0.90 +/- 0.06 nmol l-1 during 5-10 to 0.69 +/- 0.08 nmol l-1 during 10-15 years of diabetes, p < 0.05. The proportion of insulin treated patients increased from 13% (12/94) with 0-5 years of duration to 33% (13/39) with 10-15 years and 60% (18/30) with more than 15 years of duration. In conclusion in Type 2 diabetic patients without signs of autoimmunity, metabolic control, and beta-cell function deteriorate with increasing duration of diabetes, leading to common but not inevitable occurrence of 'secondary failure'.

Adult↗
PubMed1994

Glucose potentiation of arginine-induced insulin secretion is impaired in subjects with a glucokinase Glu256Lys mutation.

Insulin and glucagon release and insulin sensitivity were investigated in patients with glucokinase deficiency. Five subjects with a missense mutation (Glu256Lys) were studied. They were compared with six healthy subjects with low insulin response but normal glucose tolerance. Insulin and glucagon levels were measured at blood glucose 7.1 +/- 0.1 mmol/l and at 10.9 +/- 0.2 mmol/l with or without arginine (5 g i.v.). Insulin sensitivity was assessed as the ratio between infused glucose and the insulin level (M:I) during hyperglycemic clamps. Glu256Lys subjects were nonobese and had fasting blood glucose 6.7 +/- 0.1 mmol/l (P < 0.001 vs. control group). Insulin release was reduced in response to 11 mmol/l glucose (61% of control group, P < 0.05) as well as to arginine in the presence of 11 mmol/l glucose (54% of control group, P < 0.01). Also, the slope of potentiation, i.e., the enhancement of arginine-induced release as a function of prevailing glucose concentration, was reduced (delta insulin/delta glucose, 47% of control group, P < 0.05). As for glucagon release, the response to arginine was not inhibited normally by glucose, resulting in threefold higher levels at 11 mmol/l glucose versus control subjects. Insulin sensitivity, assessed as M:I, was significantly (P < 0.05) reduced (55% of control group). Glucokinase deficiency thus affects not only insulin responses to glucose per se but also glucose potentiation of responses to non-nutrient secretagogues. Abnormalities in glucagon release and insulin sensitivity coexist with attenuated insulin responses in glucokinase-deficient subjects.

Adult↗
PubMed1994

Impact of diabetic inheritance on glucose tolerance and insulin secretion in spontaneously diabetic GK-Wistar rats.

The impact of genetic factors and maternal diabetes on glucose tolerance and pancreatic beta-cell function was studied in first generation (F1) offspring generated in crosses between the spontaneously diabetic Goto-Kakizaki (GK)-Wistar rat and normoglycemic control Wistar rats (W). The (GK x W) F1 hybrids were offspring of either male GK (mGK) and female Wistar (fW) (mGK x fW) or male Wistar (mW) and female GK (fGK) (mW x fGK) rats. Already at 8 days of age, blood glucose levels were elevated in GK (7.6 +/- 0.5 vs. 4.8 +/- 0.3 mM in W; P < 0.001) and in F1 rats (6.0 +/- 0.3 in mGK x fW and 6.6 +/- 0.4 mM in mW x fGK; both P < 0.01 vs. W). In 2-month-old male rats, glucose (2 g/kg, intraperitoneally) markedly increased blood glucose levels after 60 min in GK rats (18.1 +/- 0.6 vs. 5.5 +/- 0.3 mM in W; P < 0.001) and moderately increased levels in F1 rats (9.9 +/- 0.9 in mGK x fW and 11.6 +/- 1.0 mM in mW x fGK, both P < 0.01 vs. W). Similar patterns were obtained in female rats. Repeated backcrossing of F1 with W rats successively improved glucose tolerance. In perfused pancreases of male rats, the 20-min insulin response to 16.7 mM glucose was -7.44 +/- 5.18 pmol in GK rats, 71.57 +/- 12.25 pmol in W rats, 9.00 +/- 0.89 pmol in mGK x fW rats, and 18.20 +/- 3.97 pmol in mW x fGK rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Autopsical observations on the blood vessels in the human lower limb.

The heterolateral femoral triangles (Scarpa's triangles, trigona femoralis) have been examined in 48 dead adult subjects of Trieste to detect relevant macroanatomical variations, performing the autopsical method. Interesting differences have been found in the topography of blood vessels, above all the arteries, from that described as normal, or better, more frequent, in the literature. The three most relevant anatomical variations for both arteries and veins are described in detail; summarizing tables and related graphics are presented for the globality of the examined cases. The percentage ratio of the observed topographic variations appears to be remarkably different when compared to their European frequency and this may be due to the exiguous number of te cases (48 subjects, that is, 96 femoral triangles) examined by us; however, the three most relevant findings have not been reported in the literature yet. Therefore, it is also reasonable to assume that the variations described in this study, either for their peculiarity or their relevant frequence, may be explained by particular functional hemodynamic needs in the examined population of Trieste, as well as by vascular developmental reasons.

Aged↗
PubMed1993

Parathyroid hormone-related protein and response to pamidronate in tumour-induced hypercalcaemia.

To find out if the concentration of parathyroid hormone-related protein (PTHrP) predicts the response of tumour-inducing hypercalcaemia (TIH) to pamidronate, we studied 44 patients. Pretreatment measurements of serum PTHrP, calcium and phosphate, nephrogenous cyclic AMP, tubular threshold for calcium and phosphate (TmP), and the presence of bone metastases were correlated with response to pamidronate. Response was considered good (normal calcium concentration corrected for albumin [CCa] for > 14 days), or poor (failure of CCa to fall, or a rise above normal < or = 14 days). PTHrP correlated significantly with response (good vs poor, p = 0.02). Undetectable PTHrP (< 2 pmol/L) was associated with a good response in all seven treatments, PTHrP in the range 2-12 pmol/L was associated with good response in 10 of 14 treatments, while PTHrP > or = 12 pmol/L was associated with a poor response in all 11 treatments. Tubular threshold for calcium correlated with the fall in CCa by day 6 after treatment (p = 0.02). Urinary clearance estimations in poor responders suggested that there was an incomplete reversal of the renal tubular component of hypercalcaemia. Serum PTHrP correlates with response to pamidronate in the treatment of TIH; which may be associated with a renal tubular mechanism not significantly affected by currently available treatment. Drugs that inhibit tubular reabsorption of calcium or PTHrP secretion may help in patients who do not respond to pamidronate.

Bone Neoplasms↗
PubMed1993

Developmental pathways of vertebral centra and neural arches in human embryos and fetuses.

The ossification pathways of both vertebral centra (i.e., vertebral bodies) and neural arches were studied in human embryos and fetuses (CR-length between 38 and 116 mm). A clearing and double-staining method for whole embryo or fetus, using alcian blue and alizarin red S, allowed an easy and precise detection of the morphology of the whole vertebral column and every single vertebra. Both cartilaginous and bony components were clearly visible. Different temporal and topographical patterns of ossification were shown for the centra and arches; the latter were respectively proximal-distal (i.e., bidirectional from a defined starting tract in T10-L1) and cranial-caudal (i.e., monodirectional). The patterns could be related to the morphogenetic processes of other structures (i.e., muscles and nerves). Moreover, the numerical survey of ossification centers provided a possible parameter for the determination of the fetal developmental age. This could be useful in the study of pathological conditions.

Alcian Blue↗
PubMed1993

B-cell insensitivity in vitro: reversal by diazoxide entails more than one event in stimulus-secretion coupling.

Sustained hyperglycemia desensitizes pancreatic B-cells to glucose. Infusion of diazoxide protects against this effect, i.e. an insulin response to glucose is preserved after exposure to the drug in vivo. The mechanisms behind this aftereffect were presently investigated in vitro. In one type of experiment, rat pancreatic islets were exposed to diazoxide (75 micrograms/ml) for 20-22 h in tissue culture. Previous exposure to diazoxide increased 2.4-fold the response to 16.7 mM glucose in final batch-type incubations. This effect was not altered by adding insulin (10 mU/ml) to the tissue culture medium. In other experiments, islets were perifused for 180 min with 27 mM glucose and, usually, 0.2 mM 3-isobutyl-1-methylxanthine. A second stimulation, 30 min long, was used to assess desensitization, which ranged between 52-80%. Diazoxide treatment during the first stimulation profoundly inhibited secretion and, as an aftereffect, completely prevented restimulation-assessed desensitization. Neither desensitization nor aftereffect were seen after low (6 mM) glucose treatment. Previous diazoxide treatment enhanced the response not only to glucose but also to 2.5 mM barium or 10 mM arginine. Desensitization induced by 30 mM potassium was not affected by diazoxide. Cooling (22 C) was employed to block glucose-induced exocytosis of insulin, but not proximal events in stimulus secretion coupling. Diazoxide treatment during cooling exerted an aftereffect that was attenuated, but not abolished (1.7-fold of the control, as assessed by restimulation at 37 C). When calcium was omitted from the perifusion medium during cooling, no aftereffect of diazoxide was seen. The results indicate that modulation of ATP-sensitive potassium channel activity is not closely linked to induction and expression of diazoxide's aftereffect, and furthermore, that protection from desensitization includes both proximal and distal events in stimulus-secretion coupling.

1-Methyl-3-isobutylxanthine↗
PubMed1993

Hypercalcemia in the blastic phase of chronic myeloid leukemia associated with elevated parathyroid hormone-related protein.

We describe a case of hypercalcemia without lytic bone lesions complicating myeloid blast crisis of chronic myeloid leukemia (CML). Serum levels of parathyroid hormone-related protein (PTHrP) were elevated during the initial hypercalcemic period and became undetectable during chemotherapy-induced chronic phase, only to become elevated again during subsequent recurrent blastic periods repeatedly associated with hypercalcemia. Previously reported cases of hypercalcemia complicating CML are reviewed. It is suggested that PTHrP was responsible for the hypercalcemia in this case and may be an important mediator of hypercalcemia in CML.

Adult↗
PubMed1992

The diabetogenic effects of glucocorticoids are more pronounced in low- than in high-insulin responders.

We investigated in six low- and six high-insulin responders (LIR and HIR) the effect of dexamethasone (Dex, 15 mg orally during 48 hr) on oral glucose tolerance (OGTT), glucose turnover under basal conditions and during glucose infusion of 2 mg.kg-1.min-1, and insulin response during hyperglycemic clamp. Dex increased fasting glucose more in LIR (P less than 0.05). During OGTT, Dex caused a more prominent increment in glucose in LIR, whereas the increment in insulin was less in LIR (P less than 0.05). After Dex, in three LIR but in no HIR, a diabetic OGTT was observed. Dex significantly increased basal hepatic glucose production (turnover measured with [6-3H]glucose), hepatic total glucose output (turnover measured with [2-3H]glucose), and glucose cycling (hepatic total glucose output--hepatic glucose production) only in LIR. Dex decreased basal glucose metabolic clearance to the same extent in LIR and HIR. Hyperglycemic clamp revealed that Dex induced a significant increase (P less than 0.05) in insulin response only in HIR. Dex effects on insulin release during hyperglycemic clamp were negatively correlated with the glucose area during Dex OGTT (P less than 0.01). Thus, the double tracer method provided a new insight into the pathogenesis of the steroid effect on carbohydrate tolerance. Dex increased basal glycemia more in LIR because only in LIR was glucose production increased. During OGTT, the LIR who were not able to counteract the effects of Dex by an appropriate enhancement in insulin secretion developed a decreased OGTT. The evaluation of insulin response after Dex may thus allow differentiation of the subset of LIR that run an increased risk of non-insulin-dependent diabetes mellitus.

Adult↗
PubMed1992

Dexamethasone treatment fails to increase arginine-induced insulin release in healthy subjects with low insulin response.

We have compared insulin responses to L-arginine before and during dexamethasone treatment in healthy subjects, previously classified as subjects with either high or low insulin response according to a standardized glucose infusion test. Arginine stimulation was administered as a 150 mg/kg bolus followed by 10 mg.kg-1.min-1 to six subjects with high insulin response and to seven subjects with low insulin response. Before dexamethasone treatment the incremental insulin level during 0-10 min of arginine was higher in subjects with high (36.5 +/- 6.8 microU/ml) than in subjects with low response (14.5 +/- 2.3 microU/ml), p less than 0.01 for difference. Dexamethasone treatment (6 mg/day for 60 h) markedly enhanced the insulin response to arginine in subjects with high response (+99% 0-30 min) but failed to affect the subjects with low response (+4% 0-30 min). The C-peptide response to arginine exhibited similar differences between groups. Decreased responsiveness to arginine in subjects with low insulin response, especially during dexamethasone treatment, suggests a Beta-cell capacity defect although a decreased potentiating-sensing effect of glucose cannot be completely ruled out.

Adult↗