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Biomedical subjects

F A Gries

Publications and source records attributed to F A Gries.

At least 91 records · Page 5Linked to original sources
PubMed1991

Visceral afferent neuropathy in diabetic gastroparesis.

OBJECTIVE: To determine whether a lack of symptoms in diabetic patients with gastrointestinal motility disorders is associated with visceral afferent neuropathy. RESEARCH DESIGN AND METHODS: We investigated cerebral evoked potentials (EPs) after esophageal stimulation in 10 patients with motor dysfunction of the gastrointestinal tract and in 10 healthy control subjects. All patients had insulin-dependent diabetes mellitus (5 men, 5 women, age range 31-60 yr, diabetes duration 8-36 yr, 10 of 10 with polyneuropathy, 6 of 10 with cardiac autonomic neuropathy). Their esophageal and gastric motor disorders had been diagnosed by scintigraphy, and gastrointestinal stenosis had been excluded by gastroscopy. Only 2 patients had severe symptoms, whereas 6 patients complained of minor discomfort (distension, bloating), and 2 patients were symptom free. RESULTS: EPs were recorded after electrical stimulation of the esophagus (32 cm from the incisors) at intensity just above the perception threshold. All control subjects exhibited regular EPs at 0.1 ms/30 mA stimulation intensity. In 6 diabetic patients, no EPs were detected at 0.1 and 0.3 ms/30 mA, and the perception thresholds were significantly elevated. In 4 patients with normal perception threshold, EPs of regular shape but decreased amplitude were recorded. These patients had mild or severe gastroparetic complaints. CONCLUSIONS: These data show for the first time an association between a lack of symptoms in diabetic gastrointestinal motility disorders and visceral afferent neuropathy.

Adult↗
PubMed1991

Determination of platelet activation by assaying filamentous actin and detecting membrane alterations.

Thrombin stimulation of human gel-filtered platelets in an unstirred system (without aggregation) results in actin polymerisation. Concomitantly with actin polymerisation the activation markers (CD 63--glycoprotein 53, a 53 kD lysosomal protein and CD 62--GMP 140, a 140 kD alpha granule protein) increase on the platelet membrane as well as the specific binding of monoclonal antibodies to thrombospondin (P 10). Consequently, both assays run in parallel and indicate sensitively platelet activation. Our data also indicate that exposure of subcellular structures following granule fusion is a very early event when platelets are challenged by thrombin and involve a reorganisation of cytoskeletal structures. Cytochalasin E inhibits completely the thrombin-induced actin polymerisation and the platelet aggregation but only partially the thrombin-induced exposure of CD 63. The activation markers CD 62 and P 10 were not influenced.

Actins↗
PubMed1990

[Diabetic nephropathy. Pathogenetic, diagnostic and therapeutic concepts].

Today the clinical picture of diabetes mellitus is often determined by its late complications. Diabetic nephropathy appears in about 40% of all diabetic patients with type 1 (insulin-dependent) diabetes mellitus within a period of 10-15 years. Early diagnosis is crucial for the prognosis as appropriate therapy may delay or even arrest the reduction of filtration fraction and terminal renal failure. Most important for the early diagnosis is the measurement of albumin and protein excretion.

Diabetes Mellitus, Type 1↗
PubMed1990

[Acute effects of extracorporeal LDL cholesterol and fibrinogen elimination on blood rheology and microcirculation].

Long-term intermittent heparin-induced extracorporeal low-density lipoprotein (LDL)-cholesterol precipitation was performed in three men - aged 32, 52 and 56 years - with severe familial hypercholesterolaemia and angiographically demonstrated coronary heart disease. This significantly lowered by 65-70% their LDL-cholesterol concentration and by 48-54% their fibrinogen concentration. Fibrinogen elimination reduced plasma viscosity by 13-14% and clearly raised the transcutaneously measured partial pressure of oxygen by 33-50%. Clinically the improved microcirculation achieved a decrease in angina symptoms: the walking distance of the 52-year-old man increased from about 100 m to 4000 m, the daily need of glyceryl trinitrate falling from an average of 12 to 4 aerosol doses.

Adult↗
PubMed1990

Flow-cytometric detection of surface membrane alterations and concomitant changes in the cytoskeletal actin status of activated platelets.

Occlusive vascular diseases are promoted by a "prethrombotic state" with increased platelet activity. Polymerization of cytoskeletal proteins and exposure of subcellular structures or rebinding of secreted proteins have been characterized as early reactions after platelet activation preceding adhesion and aggregation. Here, we demonstrate the kinetic increase in specific binding of monoclonal antibodies to thrombospondin (P10) and to platelet membrane activation markers CD63 (GP53, a 53 kD lysosomal protein) and CD62 (GMP140, a 140 kD alpha granule protein) by using a flow-cytometric bio-assay and the related change in the actin status by using the DNase-I inhibition assay after stimulation of normal human platelets with 0.2 U/ml thrombin. F-actin was raised from 41% to 51% of total platelet actin content 30 s after stimulation and remained thereafter constant (50% at 60 s). Simultaneously, the percentage of P10, CD63, and CD62 positive platelets was elevated from 5.4%, 24.4%, and 9.1% to 67.4%, 80.2%, and 82.3% respectively. The mean number of P10, CD63, and CD62 antibody binding sites increased from 3,300, 1,715, and 2,146 to 6,400, 6,800, and 9,016 per platelet. Conclusively, changes in the organization of the cytoskeletal protein "actin" and exposure of subcellular structures indicating platelet secretion can be regarded as markers of early platelet activation. Thus, the parallel response in both analytical systems provides further support for the diagnostic concept of flow-cytometric detection of preactivated platelets in the peripheral blood by using fluochrome staining procedures detecting activation dependent structural alterations directly at the cellular level.

Actins↗
PubMed1990

Proinsulin autoantibodies: association with type I diabetes but not with islet cell antibodies, insulin autoantibodies or HLA-DR type.

Antibodies reacting with proinsulin but not with insulin determinants have been observed recently in Type I diabetes. We describe here that ELISA-determined proinsulin autoantibodies (IgG-PAA) also occur in first-degree relatives of IDDM patients (38/513, 7.4% vs 1.9% in controls, P less than 0.025). In contrast to insulin autoantibodies (IgG-IAA) and islet cell antibodies (ICA) no association with HLA type was found. Furthermore, IgG-PAA occur independently of IgG-IAA and ICA. We conclude that the humoral autoimmune response to proinsulin determinants is under separate genetic control.

Autoantibodies↗
PubMed1990

Evidence for abnormal platelet glycoprotein expression in diabetes mellitus.

In 41 diabetics (27 type I, 14 type II) and in 23 healthy controls the number of glycoprotein (GP) GPIB and GPIIB/IIIA molecules were determined on resting, peripheral platelets by means of flowcytometry after immunostaining with monoclonal antibodies which bind independently from the state of activation. The average number of both glycoproteins per platelet was significantly elevated (GPIB: 54,100 x 1.27 +/- 1 vs. 39,100 x 1.3 +/- 1 GPIIB/IIIA: 77,500 x 1.3 +/- 1 vs. 62,700 x 1.3 +/- 1, in diabetic patients. Platelet volume was significantly correlated with the number of GPIB molecules on normal and diabetic platelets (r (normal) = 0.52 +/- 0.07; r (diabetic) = 0.46 +/- 0.1). Additionally, von Willebrand factor-related antigen (vWF: AG) was increased to 129% x 1.3 +/- 1 in diabetics vs. 111% x 1.4 in controls. The increase of vWF: AG was significantly correlated with HbA1 (r = 0.38*) and seemed to depend on chronic hyperglycaemia. Since platelet glycoprotein receptor status is regulated by the bone-marrow megakaryocyto- thrombopoiesis, our observations support the hypothesis that platelet hyperactivity in the diabetic state may be due to primarily altered production of platelets with an increased number of functional glycoproteins. This may be paralleled by increased plasma levels of cytoadhesive proteins like vWF: AG, which interact with the studied glycoproteins and thereby potentiate the risk of disturbed microhaemorrheology.

Adult↗
PubMed1990

Antibodies to proinsulin and insulin as predictive markers of type 1 diabetes.

The aim of the present study was to test whether proinsulin autoantibodies (IgG-PAA), insulin autoantibodies (IgG-IAA), and islet cell antibodies (ICA) may be used to identify subjects at risk for Type 1 diabetes. Pre-diabetic sera from 18 individuals who later developed diabetes were tested. Results were compared with 18 age-, sex-, and HLA-DR-matched non-diabetic control subjects from families with Type 1 diabetes. At a mean of 2.4 yr before the onset of diabetes, ICA were found in 13 patients (vs 0 control subjects, p less than 0.001), ELISA-determined IgG-IAA in 8 patients (vs 1 control subject, p less than 0.05) and ELISA-determined IgG-PAA in 4 patients (vs 2 control subjects, NS). ELISA-determined IgG-PAA do not appear to be useful predictors of the future development of Type 1 diabetes.

Adult↗
PubMed1990

Elevated platelet activation in type I diabetics with chronic complications under long-term near-normoglycemic control.

A prethrombotic state with altered, hyperactive platelets may contribute to the development of diabetic late complications. Whether increased platelet 'in vivo' activation can be reduced by tight metabolic control is controversial. We studied plasma markers of platelet activation in 64 long-term, microangiopathic type I diabetics after at least 18 months of intensive treatment for near-normoglycemia. Both platelet factor 4 and beta-thromboglobulin proved to be significantly (p less than or equal to 0.05) elevated in comparison with healthy controls: 15.8 (sdf 2)/77.6 (sdf 1.9) vs. 8.9 (sdf 1.6)/45.1 (sdf 2) ng/ml (sdf = standard deviation factor). We found no significant correlations with any metabolic parameter (actual blood glucose, mean blood glucose, HbA1, triglycerides, cholesterol) or with the duration of intensive treatment. It is therefore concluded, that platelet 'in vivo' activation takes place in type I diabetics even after long-term near-normoglycemic control. This deviation could be regarded as indicator of an additional risk for the development of vascular complications.

Adolescent↗
PubMed1990

Determination of glucose turnover and glucose oxidation rates in man with stable isotope tracers.

Determination of the turnover rates of glucose gives a more dynamic view of carbohydrate metabolism. Using 2H- or 13C-labelled glucose, stable isotope methods have been established which are free of risk for volunteers or patients and are in accordance with the legal requirements for radiation protection. The aim of the present study was to determine the main parameters of glucose turnover in vivo by using two stable-isotope-labelled glucose molecules, [6,6-2H]glucose and [U-13C]glucose. Under steady state conditions, the following parameters were analysed: glucose turnover rate, glucose oxidation rate, recycling of glucose, hepatic glucose production rate, and glucose clearance. In healthy volunteers the following data were obtained for the glucose turnover rate: 2.42 +/- 0.11 mg/kg x min, glucose oxidation rate 1.34 +/- 0.08 mg/kg x min, glucose clearance 3.04 +/- 0.17 ml/kg x min, and glucose recycling 24.7% (about 0.6 mg/kg x min). Under conditions of the euglycaemic-hyperinsulinaemic clamp (insulin levels about 80 mU/l) the glucose turnover rate increased to 9-10 mg/kg x min, and the hepatic glucose production rate was totally suppressed. Under these conditions identical glucose turnover rates were measured by rate of appearance Ra and euglycaemic-hyperinsulinaemic clamp. These data clearly demonstrate that by using differentially labelled glucose molecules at least five parameters of glucose metabolism may be determined in vivo. High insulin levels (70-80 mU/l) stimulate glucose turnover rate by 300-400%, and the glucose infusion rate agrees well with the rate of appearance (Ra) of glucose, determined with [6,6-2H]glucose. Thus, this glucose tracer provides relevant and presumably accurate data under basal and under hyperinsulinaemic conditions.

Adult↗
PubMed1989

Increased platelet volume--sign of impaired thrombopoiesis in diabetes mellitus.

Increased functional properties of diabetic platelets might be already conditioned during thrombopoiesis in the stem cell system. This hypothesis was studied by recording the distribution characteristics of the peripheral platelet pool in 218 diabetic patients versus 51 controls. Furthermore, platelet membrane coating with the stem cell marker glycoprotein IB was analyzed in 41 diabetic subjects and compared to 23 healthy volunteers. A consistent, significant shift of the volume distribution to larger platelets was found in diabetics: Mean platelet volume (MPV) - 7.9 +/- 0.9 versus 7.2 +/- 0.8 [fl]; Megathrombocyte index (MTI) - 20.4 +/- 2.8 versus 18.1 +/- 2.5 [fl]. These deviations were present in all patient subsets, however did not correlate to parameters of glucose metabolism. Whole blood platelet count was increased in the patient group; 195.0 +/- 59.5 versus 184.0 +/- 37.5 x 10(3) plts/ul. Coating with glycoprotein IB receptors correlated significantly to platelet size in platelets of both controls and diabetics (r normal = 0.52 +/- 0.07; r diabetic = 0.46 +/- 0.1). The quantitative expression of glycoprotein IB was significantly enhanced in the diabetic group: 54,500 x 1.28 +/- 1 versus 39,100 x 1.3 +/- 1 molecules per platelet. In conclusion, these findings strongly support the assumption of diabetic stem cell dysfunction of the megakaryocytic series and progenitor cells resulting in platelets with primarily increased potency to adhere and aggregate in diabetes mellitus.

Adult↗
PubMed1989

Prevalence of cytoplasmatic islet cell antibodies and insulin autoantibodies is increased in subjects with genetically defined high risk for insulin-dependent diabetes mellitus.

The presence of cytoplasmatic islet cell antibodies (ICA) and IgG insulin autoantibodies (IgG-IAA) has been observed in the prediabetic state of type 1 (insulin-dependent) diabetes (IDDM). We therefore analyzed the prevalence of these markers in sera from 1117 healthy HLA-typed first-degree relatives (1 degree Rel) of IDDM patients. ICA was determined by indirect immunofluorescence on cryostat sections of human pancreas. For IgG-IAA measurement a competitive solid-phase ELISA was used. ICA were present in 3.5% of 1 degree Rel vs 0.4% of controls (P less than 0.025). The highest frequencies of ICA were found in individuals of IDDM multiplex families (7.7%) and HLA-DR1,3 (5.4%), -DR1,4 (5.8%), and -DR3,4 (6.7%) positive subjects. We therefore conclude that the prevalence of ICA is increased in 1 degree Rel with high genetic risk for diabetes. IgG-IAA occurred in 9.9% of 1 degree Rel vs 1.4% of controls (P less than 0.01). Like ICA, IgG-IAA were significantly increased in a group of subjects being positive for either HLA-DR1,3 -DR1,4, or -DR3,4 (16.5%, P less than 0.01). In multiplex families, however, prevalence of IgG-IAA was not increased. In contrast to ICA there was an additional influence of age and sex: IgG-IAA were found more often in siblings (mean age, 16.6 years; prevalence, 15.0%) than in parents (mean age, 44.1 years; prevalence, 8.3%) of IDDM patients (P less than 0.01). In brothers the prevalence of IgG-IAA is higher than in other 1 degree Rel. Only a weak association between ICA and IgG-IAA was observed in subjects (n = 810) tested for both antibodies.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1989

Combined subtotal pancreatectomy with selective streptozotocin infusion--a model for the induction of insulin deficiency in dogs.

Standardized models of type I diabetes-like insulin deficiency in larger laboratory animals hardly exist. It was therefore investigated whether stable long-term insulin deficiency in dogs can be induced by selective beta-cell destruction in a safe and reliable procedure without damage of other organs. In Beagle dogs, the diabetogenic response to systemic streptozotocin administration (38.5-28 mg/kg b.wt.) was tested. In addition, resection of corpus and cauda pancreatis in combination with selective streptozotocin perfusion (25 mg/kg b.wt.) of the remaining pancreas tissue was evaluated. Whereas systemic streptozotocin administration failed to destroy insulin secretion, but led to a variety of intoxication symptoms even in comparatively low doses (28 mg/kg b.wt.), the latter procedure resulted in a complete and persistent insulin depletion (basal serum immunoreactive insulin less than or equal to 3 microU/ml, no stimulated response) without toxic organ damage or other serious side effects. The dogs developed type I-like diabetes, which required continuous exogenous insulin substitution. From these results, subtotal pancreatectomy with selective streptozotocin perfusion of the remaining pancreas is proposed as a safe model of insulin deficiency in dogs, which should be further evaluated in experimental diabetology.

Animals↗
PubMed1988

The natural course of peripheral and autonomic neural function during the first two years after diagnosis of type 1 diabetes.

Motor and sensory nerve conduction velocities (MNCV, SNCV), beat-to-beat variation (BBV) at rest, speed of pupillary dilation (SPD), and pupillary latency time (PLT) were measured in 32 patients aged 12-36 years after 19 +/- 2 (mean +/- SEM) days and again after 3, 12, and 24 months of insulin treatment. Moreover, BBV under deep respiration was determined after 12 and 24 months, and thermal discrimination thresholds (TDT) as well as pain and vibration perception thresholds (PPT; VPT) were evaluated after 24 months. Mean HbA1 levels during months 3-24 within the normal range (7.2 +/- 0.2%; mean +/- SEM) were observed in 20 patients (group 1), while in 12 patients (group 2) mean HbA1 of months 3-24 was elevated (10.1 +/- 0.4%). There were no significant differences between both groups with regard to the nerve function tests at baseline and after 3 months. After 12 months mean median MNCV and median, ulnar, and sural SNCV were significantly lower in group 2 than in group 1 (p less than 0.05). After 24 months mean median MNCV, peroneal MNCV, median SNCV, and sural SNCV as well as both BBV tests and PLT were significantly impaired in group 2 as compared to group 1 (p less than 0.05). In addition, mean malleolar VPT and PPT to heat and cold stimuli on the thenar and the foot were significantly elevated in group 2 as compared to group 1 (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗