[Therapy of primary biliary cirrhosis].
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Chronic Disease↗
Biomedical subjects
R Klein
Publications and source records attributed to R Klein.
Correlation between the synergistic effect of liposomes and endotoxins on the activation of macrophage tumoricidal activity and the effect of liposomes on the rough endoplasmic reticulum of macrophages.
Treatment of resident peritoneal macrophages of rats with small unilamellar vesicles of dipalmitoylphosphatidylcholine (DPPC SUV) potentiated their activation for tumor cell lysis by endotoxins. The fluorescence polarization of diphenylhexatriene (DPH) embedded in rough endoplasmic reticulum membranes isolated from DPPC SUV-treated macrophages was enhanced. The average fluorescence lifetime of DPH and the rotational correlation time deduced from anisotropy decay were unchanged, whereas the residual anisotropy and hence the order parameter were increased. The measurement of the fluorescence anisotropy of DPH as a function of the temperature showed a phase transition. No phase transition was observed in the rough endoplasmic reticulum membranes of macrophages either treated or not treated with cholesterol/DPPC SUV (1/1; mol/mol). The synergistic effect of DPPC SUV on the tumoricidal activity of macrophages induced by endotoxins appears to be correlated with the changes in the properties of the rough endoplasmic reticulum membranes. Both effects were transient; they had the same kinetics of induction and reversion, and they were both inhibited by cholesterol.
1,2-Dipalmitoylphosphatidylcholine↗
The effect of intravenously injected beta very low density lipoprotein on small and large arterial injuries.
A series of daily injections of beta very low density lipoprotein (beta-VLDL) was administered over 4-5 days to rabbits whose arteries contained either experimental circumferential lesions or areas of intimal thickening. The circumferential lesions were similar to those that occur spontaneously and were produced by the application of longitudinal tension. The intimal thickening was produced by denuding the endothelium with a balloon catheter. Over the period of injection of beta-VLDL the plasma cholesterol levels rose in a pulse-like manner from 60 to 100 mg/dl. Following cessation of injections the cholesterol levels initially rose further and then decreased to normal levels within 4 weeks. Injections of beta-VLDL, commencing 1-2 days after production of the circumferential lesions, resulted in an increase in the number of mononuclear leukocytes (primarily macrophages) and in a moderate accumulation of lipid by these cells and the medial smooth muscle cells. If the injections were started 14 days postinjury there was some accumulation of lipid in the large lesions but none in small lesions. There was no lipid accumulation in any lesions if the beta-VLDL was administered 3 months postinjury or if the animals were injected 2 days after injury and examined 3 months later. A very slight accumulation of lipid occurred in the intimal thickening, or neo-intima, following a series of beta-VLDL injections given to rabbits 2 or 6 weeks after balloon catheter injury. The series of injections produced a significant increase in the number of mononuclear leukocyte profiles per area of the neo-intima, suggesting an increased infiltration of these cells into the injured artery. These results suggest that a small transient increase in the plasma concentration of cholesterol-carrying lipoproteins may lead to increased infiltration of mononuclear leukocytes into areas of intimal thickening or areas of "spontaneously occurring" injury.
Animals↗
Highly glycosylated PDGF-like molecule secreted by simian sarcoma virus-transformed cells.
Antiserum to human platelet-derived growth factor (PDGF) recognized a simian sarcoma virus transformation-specific glycopeptide, now termed gp200sis, thereby establishing an immunological relationship between PDGF and this highly glycosylated molecule. The same antibodies as well as an antiserum against SSV-NP cells reacted with isolated gp200sis after immunoprecipitation, SDS-PAGE, and electroelution. In analogy to PDGF, the gp200sis protein backbone is shown here to consist of disulfide-linked polypeptide chains. On SDS-PAGE under nonreducing conditions, the deglycosylated molecule migrated as two dimers with molecular weights of 26 and 28 kDa, respectively. Preliminary functional studies indicate that SSV nonproducer cells secrete high-molecular-weight mitogens (greater than 150 kDa) that are specific for SSV-induced transformation. We suggest that gp200sis acts as a PDGF-like growth factor.
Cell Transformation, Viral↗
Visual field differences in the processing of numerical stimuli.
Twenty-four right-handed subjects received random presentations of the numbers 1-6 in the form of words, digits, and dot patterns, to the left and right visual fields. Accuracy and reaction time were recorded for an odd-even judgment requiring a manual response. A significant stimulus type of visual field interaction was obtained, with words showing a left-hemisphere advantage and digits and dot patterns showing a right-hemisphere advantage. This pattern supports Coltheart's (1980, Deep dyslexia: A right hemisphere hypothesis, In M. Coltheart, K. Patterson, & J.C. Marshall (Eds.), Deep dyslexia, London: Routledge & Kegan Paul) right hemisphere reading hypothesis, which suggests that the left hemisphere's general advantage in processing linguistic material may be specific to stimuli which involve phonological processing. When phonological processing is not possible (e.g., for arabic digits and other ideographic orthographies), the right hemisphere may have an advantage because of its superior visuospatial processing capabilities.
Cerebral Cortex↗
Methodologic considerations in measuring glycosylated hemoglobin in epidemiologic studies.
Multiple linear regression was used to predict an incubated glycosylated hemoglobin value from the unincubated value and blood glucose. Hemoglobin A1 (HbA1) was measured by a disposable microcolumn technique in a large, geographically defined population of diabetic persons in southern Wisconsin. During the study, incubation of blood samples to remove pre-A1c was implemented. Multiple linear regression using data from a group of 788 patients yielded the equation: incubated HbA1 = 0.897 (non-incubated HbA1)-0.00332 (blood glucose) + 0.388. This equation was "validated" by substituting the calculated value of incubated HbA1 for the actual value in a multinomial logistic regression with diabetic retinopathy as the dependent variable. Little change in the model resulted from the substitution. Further validation was obtained from an independent sample of diabetic persons. Calculated values of incubated HbA1 were an average of 0.4% lower than the actual values.
Age Factors↗
Recent developments in the understanding and management of diabetic retinopathy.
The natural history of diabetic retinopathy, one of the leading causes of visual impairment in the United States, is well described; its pathogenesis, however, is poorly understood. The Diabetic Retinopathy Study and the Early Treatment of Diabetic Retinopathy Study have demonstrated that timely intervention with photocoagulation prevents visual loss. However, recent studies demonstrate that many diabetic patients are not being referred to ophthalmologists for timely treatment. Suggested management and referral strategies are presented in this article.
Adolescent↗
The incidence of vision loss in a diabetic population.
The 4-year incidence of blindness and vision loss was examined in a population-based study of diabetes mellitus. In subjects participating in baseline and 4-year follow-up examinations, the rate of blindness was 1.5, 3.2, and 2.7% in younger onset persons, older onset persons taking insulin, and older onset persons not taking insulin, respectively. The rate of blindness increased with increasing age, increasing diabetic retinopathy severity, and lower baseline visual acuity in all three groups. Blindness increased with increasing duration of diabetes in younger onset persons and older onset persons taking insulin. The incidence of vision loss, as measured by a doubling of the visual angle, was associated with older age, more severe retinopathy, and presence of macular edema in the three groups. It was also associated with duration of diabetes, presence of proteinuria, and higher glycosylated hemoglobin in younger onset and older onset persons taking insulin.
Adolescent↗
The antimitochondrial antibody anti-M9. A marker for the diagnosis of early primary biliary cirrhosis.
The clinical relevance of a new antimitochondrial antibody, anti-M9, reacting with an outer membrane-associated antigen on liver mitochondria is described. Sera from 22 anti-M2-negative patients with histologically proven primary biliary cirrhosis (PBC) who had been followed for 5-15 years were tested for anti-M9 in the ELISA using a purified M9-fraction. 18 (82%) were anti-M9-positive, and 17 of them (94%) were in stage I/II. None of the 17 anti-M9-positive/anti-M2-negative patients with early PBC progressed to stage III/IV during the observation period of 5-15 years, and in all instances anti-M9 remained of the IgM-type. In one anti-M9-positive patient anti-M2 of the IgM type appeared 2 years after the first demonstration of anti-M9. Among 156 patients with anti-M2-positive PBC, 58 (37%) had anti-M9, and 39 of them (67%) were in stage I/II. 19 of these 39 stage I/II patients (49%) had anti-M9 exclusively of the IgM-type in contrast to none of the 19 stage III/IV patients. Using the purified M9-fraction in ELISA and Western blotting, anti-M9 antibodies were confined only to patients with PBC or overlap syndromes between PBC and autoimmune chronic active hepatitis (10% of 133 patients) and were not found in patients with other hepatic and non-hepatic disorders. We conclude that the determination of anti-M9 may be helpful for the diagnosis of early and asymptomatic PBC. From follow-up studies of anti-M9-positive but anti-M2-negative patients it emerges that this antibody type may be associated with a benign course of PBC.
Antibody Specificity↗
The 89,000-Mr murine cytomegalovirus immediate-early protein stimulates c-fos expression and cellular DNA synthesis.
The immediate-early (IE) genes of murine cytomegalovirus (MCMV) are expressed in the absence of prior viral protein synthesis and regulate the transcription of MCMV early genes. The effect of MCMV IE genes on growth induction was studied. Different plasmids containing MCMV IE genes were microinjected into arrested NIH 3T3 mouse fibroblasts. Plasmids containing the ieI gene coding for the 89,000-Mr major IE protein pp89 were found to stimulate the expression of the c-fos protooncogene. Synthesis of pp89 and its transport to the nucleus appeared to be required for c-fos expression. DNA synthesis occurred in cells that were injected with MCMV IE genes and in neighboring cells that were not injected. The results suggest that the phosphoprotein pp89 stimulates cells to enter the cell cycle.
Animals↗
Hemodynamics, circulating catecholamines and response to intravenous nitrate therapy in a specific subset of acute myocardial infarction: the hypertensive-hyperkinetic-coronary-active group.
A specific subset of acute myocardial infarction was defined and named 'the hypertensive-hyperkinetic-coronary-active' subgroup. This subgroup included patients with acute myocardial infarction without pump failure or hypovolemia who continued to have hypertension and tachycardia, after relief of pain and who also had at least two recurrent ischemic episodes in the first days after a transmural event. Fifteen patients belonging to this group (group A) were studied in comparison with 15 other patients with acute myocardial infarction complicated by pump failure (group B). The alterations in hemodynamics, in circulating catecholamine levels and the clinical course during an intravenous infusion of isosorbide dinitrate were evaluated and the data obtained in the two groups were compared. The patients in group A had tachycardia, hypertension and upper normal filling pressures (pulmonary capillary wedge pressures: 15.8 +/- 1.8 mm Hg). They had high levels of circulating catecholamines (1,343 +/- 407 ng/l), a cardiac output of 5.9 +/- 0.6 liters/min and stroke work index of 78 +/- 11 (mean +/- SD). The effect of intravenous nitrates on the left ventricular function curves of the two groups was the following: a marked shift downward and slight shift to the left in group A, as opposed to a moderate but significant shift upward and marked shift to the left in group B. The episodes of recurrent ischemia subsided in 13 out of 15 patients from group A. It appears therefore that the hyperkinetic patients with acute infarction are characterized by a hypersympathetic response, a typical hemodynamic profile and a particular response to nitrate therapy directionally opposite to the changes obtained in patients with acute infarction complicated with failure.
Aged↗
Elevated CK-MB isoenzyme after exercise stress test and atrial pacing in patients with ischemic heart disease.
Using a highly sensitive monoclonal antibody kit for CK-MB, significant release of small amounts of CK-MB isoenzyme after exercise stress test was detected 4 to 6 h after induction of ischemia. This occurred in ten out of 15 patients with ischemic heart disease (66 percent) and in only one of the 18 healthy subjects (5.6 percent) serving as a control group. In five patients with coronary artery disease in whom atrial pacing was performed with simultaneous blood sampling from coronary sinus, a drastic elevation in CK-MB isoenzyme (from 2.04 +/- 2.06 ng/L to 10.88 +/- 6.9 ng/L; p less than 0.001) was detected within 10 to 30 min after induction of acute ischemia. A small but significant increase in total CK also was detected (from 21 +/- 12 IU/L to 52 +/- 14IU/L; p less than 0.01). These preliminary observations have to be further investigated in a larger group of patients before a definitive conclusion can be reached about the clinical significance of CK-MB release during exercise.
Adult↗
Diabetic retinopathy in Mexican Americans and non-Hispanic whites.
Mexican Americans (MAs) have a threefold greater prevalence of non-insulin-dependent diabetes mellitus (NIDDM) than non-Hispanic Whites (NHWs). Because MA diabetic subjects have greater hyperglycemia and an earlier age of onset than NHW diabetic subjects, we postulated that diabetic MAs might also have more severe diabetic retinopathy. Stereoscopic retinal photographs of the seven standard fields of each eye were taken in 257 MAs and 56 NHWs with NIDDM. The photographs were read by the University of Wisconsin Fundus Photographic Reading Center and graded with standardized criteria. The MAs had a nonsignificantly increased risk of retinopathy relative to the NHWs [odds ratio (OR) = 1.71; 95% confidence interval (Cl) = (0.93, 3.17)]. The risk of severe retinopathy (proliferative or preproliferative) relative to background or no retinopathy was significantly greater in MAs than in NHWs [OR = 2.37; 95% Cl = (1.04, 5.39)]. After control by logistic regression for duration of disease, severity of hyperglycemia, age, and systolic blood pressure, MAs still had an increased risk of severe retinopathy relative to NHWs [OR = 3.18; 95% Cl = (1.32, 7.66)]. Severe retinopathy was related to duration of disease, hyperglycemia, and insulin therapy in both ethnic groups. Previously diagnosed MA diabetic subjects also had an increased prevalence of any retinopathy [OR = 2.39; 95% Cl = (1.63, 3.50)] and severe retinopathy [OR = 3.21; 95% Cl = (2.24, 4.59)] relative to previously diagnosed White diabetic subjects (n = 896) from Wisconsin.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Inherited susceptibility to insulin-dependent diabetes is associated with HLA-DR1, while DR5 is protective.
Of the HLA allelic associations with insulin-dependent diabetes (IDD) reported to date. DR3 and DR4 have been the most positive and DR2 the most negative. In 952 Caucasian proband patients reported here, only 57 or 6% had no DR3 or DR4 alleles. When these 57 patients were compared to 249 Caucasian controls similarly lacking DR3 and DR4 antigens, there were excesses of DR1 (P = 0.13) and DRW8 (P = 0.01) and deficiencies of DR2 (P = 0.03) and DR5 (P = 0.03) in the patient group. The most common phenotype in this group of patients was DR1/DR7 (12.3%). Only four DR-homozygous patients involving alleles other than DR3 and DR4 were found by genotyping, and all were DR1 homozygotes. Among 506 patients wuth DR3/DRX or DR4/DRX phenotypes, DR1 was more frequent (P = 0.001; Bonferronni P = 0.006), and DR2 (P = 0.001) and DR5 (P = 0.001) less frequent than 243 HLA-matched controls. Of 187 patients with a single DR3 and no DR4, DR1 was more frequent (P = 0.02), with DR2 (P = 0.001) and DR5 (P = 0.02) less frequent than 94 HLA DR-compatible controls. Among 319 patients with a single DR4 but no DR3, DR1 was again more frequent (P = 0.01) and DR2 (P = 0.001) and DR5 (P = 0.001) less frequent than 149 HLA-matched controls. We conclude that DR1 is an additional risk DR allele for IDD to that of DR3 and DR4, and DR5 an additional protective DR allele to that of DR2.
Adolescent↗
Characterization of a new mitochondrial antigen-antibody system (M9/anti-M9) in patients with anti-M2 positive and anti-M2 negative primary biliary cirrhosis.
A new antimitochondrial antibody (AMA) against an outer membrane associated antigen on liver mitochondria was detected by ELISA in sera from patients with primary biliary cirrhosis (PBC). This antibody was named anti-M9. There is evidence that it is a partial organ-specific antibody as shown by absorption studies using submitochondrial particles prepared from heart, liver and kidney. A purified M9-fraction was prepared by subjecting a 100,000 g supernatant from rat liver mitochondria to ion exchange chromatography. This fraction was devoid of the previously described M1-M8 antigens except for M4. Trypsin treatment of the fraction enabled a distinction to be made between M4 which was protease resistant, and M9 which was trypsin sensitive. Applying this M9-fraction in Western blotting anti-M9 positive sera recognized two proteins at a molecular weight of 98 kD and 59 kD. Anti-M9 antibodies were detected in 37% of 156 anti-M2 positive as well as in 82% of 22 anti-M2 negative patients with histologically proven PBC. It is concluded that anti-M9 is a new AMA type in PBC which may be helpful especially for the early diagnosis of PBC in patients who are still anti-M2 negative. As one of the earliest immunological signs in PBC further characterization of M9 could provide new insights into the etiopathogenesis of the disease.
Antibodies↗
A high-molecular-weight PDGF-like factor secreted by v-sis transformed cells leads to growth stimulation and transformation.
Transformation by the v-sis containing simian sarcoma virus (SSV) is believed to be mediated by constitutive production of a platelet-derived growth factor (PDGF)-like molecule and its interaction with the PDGF receptor. SSV-transformed nonproducer NRK cells release into their tissue culture supernatant a high-molecular-weight factor (150-300 kDa) with biological activities closely resembling those of human PDGF. The partially purified high-molecular-weight factor competes with 125I-PDGF for receptor binding and leads to growth stimulation and anchorage-independent growth of normal cells. All these activities can be blocked by antibodies against PDGF and SSV-NP cells. The formerly described SSV transformation-specific glycopeptide (Thiel and Hafenrichter, 1984), now termed gp200sis, is recognized by the same specific antibodies and shows a striking resemblance in size. We conclude that gp200sis is responsible for the described PDGF-like activities.
Animals↗
Proteinuria in diabetes.
In a population-based study in southern Wisconsin, 1370 diabetic persons diagnosed after 29 years of age were examined using standard protocols to determine the prevalence of proteinuria and associated risk variables. Proteinuria (greater than or equal to 0.30 g/L) was present in 18.0% of persons taking insulin and 12.2% of the persons not taking insulin. Proliferative retinopathy and proteinuria were associated with each other. Proteinuria was also associated with increasing duration of diabetes, high systolic blood pressure, use of digoxin, and being male, but not with a history of cigarette smoking or metabolic control as measured by glycosylated hemoglobin.
Adult↗
The isolation of polypeptides with FSH suppressing activity from bovine follicular fluid which are structurally different to inhibin.
Three proteins (31, 35 and 39 kDa) with inhibin-like activity have been isolated from bovine follicular fluid with identical NH2-terminal amino acid sequences. These polypeptides are distinct from inhibin, based on their different NH2-amino acid sequence, molecular masses, absence of a subunit structure, absence of inhibin immunoactivity and the failure of inhibin antiserum to neutralize their bioactivity in vitro. Their inhibin-like biological activities based on their ability to suppress FSH cell content by pituitary cells in culture are 5-10% of bovine 31 kDa inhibin.
Amino Acid Sequence↗