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Biomedical subjects

A Friedman

Publications and source records attributed to A Friedman.

At least 163 records · Page 9Linked to original sources

Intraportal hyperinsulinemia decreases insulin-stimulated glucose uptake in the dog.

Hyperinsulinemia and insulin resistance are commonly seen in obese and non-insulin-dependent diabetes mellitis (NIDDM) patients. While it is known that chronic exposure to severe hyperinsulinemia can lead to an insulin-resistant state and mild hyperinsulinemia for rather short durations (20 to 40 hours) and can also lead to insulin resistance, it is less clear whether mild hyperinsulinemia for a more prolonged duration can lead to insulin resistance. In the present study we determined the effects of chronic (28 days) exposure to mild hyperinsulinemia on insulin-stimulated glucose use. Chronic hyperinsulinemia was produced by an intraportal infusion of porcine insulin (425 microU/kg/min), which raised the basal peripheral insulin levels by approximately 50%. Insulin responsiveness was assessed using the euglycemic hyperinsulinemic clamp (2 mU/kg/min) in dogs before the induction of chronic hyperinsulinemia (day 0), after 28 days of hyperinsulinemia (day 28), and 28 days after discontinuation of the chronic insulin infusion (day 56). The amount of glucose (M) required to maintain euglycemia during the euglycemic hyperinsulinemic clamp was decreased (relative to day 0) 39% +/- 3% on day 28 and 18% +/- 3% on day 56 (P less than .05). In control animals that received a chronic infusion of saline for the 28-day period the glucose infusion rate (M) was not changed significantly (decreasing 2% +/- 5% and 5% +/- 10% on days 28 and 56, respectively). In conclusion insulin resistance can be produced by a mild hypersecretion of insulin and discontinuation of the chronic insulin infusion tends to reverse the resistance.

Animals↗

Seeing versus imagining movement in depth.

Subjects judged the quality of rigid motion between pairs of three-dimensional drawings that differed by a rotation in depth. The figures were aligned with, and rotated around, either the vertical axis or an axis that was oblique with respect to the XYZ co-ordinate system. Rated quality of motion decreased with increasing angular disparity between the figures and with decreasing stimulus duration, regardless of whether the figures were vertical or oblique. The same subjects then participated in a mental rotation task using the same stimuli and angular disparities. An effect of principal axis emerged, such that subjects took longer to make decisions about obliquely aligned stimuli than about vertically aligned stimuli, especially if they received the oblique stimuli first. These data imply that perceived versus imagined movement through the same trajectory involves different processes. Whereas the apparent motion system performs its computations relatively automatically, the processes involved in mental rotation are more strategic in nature.

Adult↗

The role of the CCAAT/enhancer-binding protein in the transcriptional regulation of the gene for phosphoenolpyruvate carboxykinase (GTP).

Previous studies have identified a region in the promoter of the gene for phosphoenolpyruvate carboxykinase (GTP) (PEPCK) (positions -460 to +73) containing the regulatory elements which respond to cyclic AMP, glucocorticoids, and insulin and confer the tissue- and developmental stage-specific properties to the gene. We report that CCAAT/enhancer-binding protein (C/EBP) binds to the cyclic AMP-responsive element CRE-1 as well as to two regions which have been previously shown to bind proteins enriched in liver nuclei. The DNase I footprint pattern provided by the recombinant C/EBP was identical to that produced by a 43-kDa protein purified from rat liver nuclear extracts, using a CRE oligonucleotide affinity column, which was originally thought to be the CRE-binding protein CREB. Transient contransfection experiments using a C/EBP expression vector demonstrated that C/EBP could trans activate the PEPCK promoter. The trans activation occurred through both the upstream, liver-specific protein-binding domains and the CRE. The CRE-binding protein bound only to CRE-1 and not to the upstream C/EBP-binding sites. The results of this study, along with physiological properties of C/EBP, indicate an important role for this transcription factor in providing the PEPCK gene with several of its regulatory characteristics.

Animals↗

A gastrin-releasing peptide antagonist containing A psi (CH2O) amide bond surrogate.

The [Leu26-psi(CH2O)Leu27] derivative of N-Ac-GRP20-27-peptide amide was prepared and evaluated as a gastrin-releasing peptide antagonist. This psi(CH2O) derivative was found to be a more potent inhibitor of [3H-Phe15]GRP15-24NH2 binding and N-Ac-GRP20-27NH2 induced mitogenesis in Swiss 3T3 fibroblasts than the related nitrogen analog [Leu13-psi(CH2NH)Leu14] bombesin. Possible reasons for the improved activity of the (CH2O) insert relative to the (CH2NH) group include increased hydrophobicity and a reduced tendency of the oxygen derivative to form hydrogen bonds.

Amino Acid Sequence↗

Carboxyl-terminal modification of a gastrin releasing peptide derivative generates potent antagonists.

Gastrin releasing peptide (GRP) is a 27-residue peptide hormone which is analogous to the amphibian peptide bombesin. GRP serves a variety of physiological functions and has been implicated as an autocrine factor in the growth regulation of small cell lung cancer cells. We have developed a series of potent GRP antagonists by modification of the COOH terminus of N-acetyl-GRP-20-27. The most potent member of this series, N-acetyl-GRP-20-26-OCH2CH3, exhibits an IC50 of 4 nM in a competitive binding inhibition assay. This compound blocks GRP-stimulated mitogenesis in Swiss 3T3 mouse fibroblasts, inhibits GRP-dependent release of gastrin in vitro, and blocks GRP-induced elevation of [Ca2+]i in H345 small cell lung cancer cells. These results demonstrate that while residues 20-27 of GRP influence binding of the parent peptide to its receptor, the COOH-terminal amino acid is primarily responsible for triggering the subsequent biological response.

Amino Acid Sequence↗

Familial hemifacial spasm.

We present a family in which hemifacial spasm involving in all cases the left side of the face occurred in five persons in three generations. Blink reflexes recorded in two cases demonstrated an unexpected R1 component on the affected side during stimulation of the contralateral side.

Adult↗

Ultrasonic prediction of growth discordancy by intertwin difference in abdominal circumference.

Intertwin abdominal circumference (AC) and femur length (FL) differences were studied in 24 growth-discordant (greater than or equal to 15% birth weight difference) and in 32-growth concordant twin pairs delivered within 2 weeks of the last ultrasonic examination. Both groups were of similar gestational age but differed significantly in the mean twin birth weight and intertwin AC difference (P = 0.01 and P = 0.00009, respectively). A cutoff value (greater than or equal to 18 mm) for AC difference was found to discriminate significantly (P less than 0.0009) between concordant and discordant pairs with sensitivity, specificity, positive predictive value and negative predictive value of 66.7%, 78%, 69.5% and 75.7%, respectively. These data may suggest that an intertwin difference of 18 mm or more in AC effectively screens for the diagnosis of 15% or more birth weight difference in twin pregnancies.

Abdomen↗

Sex-related differences in immune response and survival rate of broiler chickens.

In a comparison between male and female broiler chicks, the mortality rate of males was found to be significantly higher than that of females, starting from the second week of age until marketing at 7 or 8 weeks of age. The main causes of death during this period were various infectious diseases. This observation was explained by differences in the activity of humoral and cell-mediated immune responses between the sexes. In tests of antibody responses of young chicks to a variety of antigens (bacterial-E. coli, viral-Newcastle disease virus, and protein antigen-bovine serum albumin), females responded 24-72 h earlier than males and with higher peak antibody titers. In-vitro proliferation of T-lymphocytes to purified protein derivative and E. coli showed an earlier and greater response in females. The correlation between immune responsiveness and survival, as tested by challenging vaccinated chicks with pathogenic E. coli, showed a significantly higher mortality rate in vaccinated males, that was correlated with their lower antibody titer. We concluded, therefore, that sex-related differences in mortality rates of broiler chicks may result from a less efficient immune response in males.

Aging↗

Vaccination against experimental autoimmune encephalomyelitis using a subencephalitogenic dose of autoimmune effector T cells. (2). Induction of a protective anti-idiotypic response.

We previously reported that a subencephalitogenic dose (10(4) of activated anti-BP Z1a T cells rendered Lewis rats significantly resistant to EAE induced either actively or adoptively. This resistance was specific to EAE and persisted for over 4 months. The experiments reported in this paper were done to investigate the mechanisms of this resistance. We found that the state of vaccination was marked by a decrease in the in vitro proliferation and in vivo DTH responses to BP. Resistance could be transferred to recipient rats with the thymus or spleen cells of donor vaccinated rats. Vaccination led to the appearance of proliferative and DTH responses that were specifically directed to the Z1a T cells. The kinetics and compartmentalization of this anti-idiotypic responsiveness was studied by vaccinating rats in the hind footpads and monitoring the proliferative reactivity of the draining popliteal lymph node (PLN) and distal cervical lymph node (CLN) cells at various times. We found that the anti-idiotypic reactivity was confined to the PLN on days 5-6 and thereafter became systemic. Excision of the PLN on day 6, but not on days 3 or 11, robbed the rats of their acquired resistance to EAE. In contrast, the PLN cells of the vaccinated rats transferred resistance to naive donors. Thus, the lymphoid population containing cell-mediated anti-idiotypic responsiveness served as a vehicle of resistance. These results suggest that anti-idiotypic T-cell immunity to autoimmune effector T cells is involved in the resistance to EAE induced by T-cell vaccination.

Animals↗

Rapid determination of total hydroxyproline (HYP) in human urine by HPLC analysis of the phenylisothiocyonate (PITC)-derivative.

A recent development in the preparation for amino acid analysis is the use of phenylisothiocyanate (PITC) as a precolumn derivatizing agent prior to analysis to form a stable derivative. These derivatives can then be separated by reversed phase high pressure liquid chromatography (HPLC). Because of interest in the accurate measurement of urinary hydroxyproline (HYP), PITC was used for derivatization followed by HPLC analysis. Using an automated computer-controlled sampler system, up to 75 samples can be analyzed each 24 h. Technical details, specificity, and reliability of this method are provided. Duplicate measurements of HYP had a coefficient of variation (CV) of 5.5% and with a recovery of HYP in spiked urine samples of 94 to 104%. A sample frozen and thawed 10 times showed no change in the concentration of HYP. When total HYP was measured in 230 healthy women between 20 and 39 years of age, it was found to be 236.62 +/- 146.41 mumoles/L. These samples were researched in 3.5 days using this technique.

Adult↗

Impaired T lymphocyte immune response in vitamin A depleted rats and chicks.

Vitamin A deficiency results in decreased immune responses; the objective of the present study was to investigate the involvement of T lymphocytes in the depression of immune responses resulting from vitamin A depletion. This objective was achieved by evaluating antigen-specific T lymphocyte proliferative responses in vitro as vitamin A depletion developed. The evaluation was performed in both rat and chick to examine the generality of immune effects due to vitamin A depletion. Our findings show that vitamin A depletion led to severe impairment of T lymphocyte activity in both animal models, and that this was directly related to the vitamin A status in both species. Immune response impairment was found to precede other manifestations of vitamin A deficiency, and was rapidly corrected by feeding retinyl acetate boluses. This implied a possible regulatory, rather than constitutive, role of vitamin A in immune responsiveness.

Animals↗

Recovery of ova and their re-insertion into the hen's oviduct through a fistula.

1. The first loop of the domestic hen's magnum was fistulated. A cannula mounted with a collecting tube served to trap the passing ova about 2.5 h following ovulation. 2. Nine out of 10 fistulated hens resumed ovulation about 2 to 5 weeks following surgery. A total of 63 magnal ova were collected. 3. Five of the magnal ova were successfully returned to the oviduct through the fistula and resulted in 5 normal soft-shelled eggs. The success of ova reimplantation was affected by prolapse of the posterior part of the oviduct and the timing of ova return.

Animals↗

Antigen-specific immune response impairment in the chick as influenced by dietary vitamin A.

The effects of a broad range of dietary vitamin A levels on antigen-specific immune responses of the chick were studied. Vitamin A deficiency and long-term excess caused impairment of the immune response as demonstrated by antigen-specific antibody production and T-lymphocyte proliferation in vitro. Immune responsiveness was correlated with both hepatic and blood vitamin A levels, and was affected prior to other physiological manifestations of hypo- or hypervitaminosis. In contrast to the effects of long-term vitamin excess, a large vitamin A bolus did not cause immune response impairment and, on the contrary, restored normal immune functions in previously vitamin A-depleted chicks. This finding implied a regulatory role for vitamin A in the immune system rather than a constitutive one.

Animals↗

Comparison of hemodynamic, electrocardiographic, mechanical, and metabolic indicators of intraoperative myocardial ischemia in vascular surgical patients with coronary artery disease.

To compare mechanical, electrocardiographic, and metabolic indices of myocardial ischemia, the cardiokymogram (CKG), the V5 ECG, left anterior descending coronary artery territory lactate extraction, and pulmonary capillary wedge pressure (PCWP) were measured in 53 vascular surgical patients with coronary artery disease. Measurements were performed preoperatively and at four specific intraanesthetic intervals: after tracheal intubation, before surgery, and 10 and 30 min after incision. Measurements and sampling sequence took 5-7 min, and therapy for the probable cause of ischemia was instituted following completion of this sequence. Myocardial ischemia was defined as type II or III CKG, 0.1 mV or greater horizontal or downsloping depression of V5 ECG ST segment, 0.2 mV or greater elevation of V5 ECG ST segment, or myocardial lactate production. Thirty-nine patients (74%) had a total of 89 episodes of myocardial ischemia. Seventy-four episodes (83%) were detected by the CKG, 31 (44%) were evident on the ECG, and 13 (15%) by evidence of lactate production. The concordance among the indices of myocardial ischemia was poor. Patients with an abnormal preoperative ECG experienced a greater number of ischemic episodes (P less than 0.001). Elevation of PCWP or the presence of A-C or V-waves greater than 5 mmHg above the mean did not individually reflect ischemia reliably. Intraoperative myocardial ischemia is common in vascular surgical patients and is most sensitively detected by ventricular wall motion abnormality.

Aged↗

Neuroblastoma: imaging evaluation by sequential Tc-99m MDP, I-131 MIBG, and Ga-67 citrate studies.

Fourteen children with histopathologically confirmed neuroblastoma underwent sequential correlative imaging studies using I-131 MIBG, Tc-99m MDP, and Ga-67 citrate during various stages of the disease. Of the patients 86% showed I-131 MIBG accumulation in the primary tumoral site, whereas 71% showed Tc-99m MDP and 79% Ga-67 citrate uptake. In 86% at least one of the two latter radiopharmaceuticals concentrated in the primary tumor. The use of all three radiopharmaceuticals raised the detection rate to 93%. Of the osseous or extraosseous metastases 100% were detected by Tc-99m MDP studies. The I-131 MIBG studies were positive in 71% of the osseous metastases and in 70% of the extraosseous metastases. No Ga-67 citrate uptake was demonstrated in osseous metastases, although one extraosseous lung metastasis concentrated this radiopharmaceutical. Tc-99m MDP bone imaging was the best method for diagnosing metastatic spread of the disease and for monitoring the results of treatment. Primary tumor uptake was best indicated by I-131 MIBG. Both Ga-67 citrate and I-131 MIBG were superior to Tc-99m MDP with regard to accurately demonstrating the extent of primary tumors. Only Tc-99m MDP indicated the relationship of these tumors to the kidneys and neighboring osseous structures, providing early screening of kidney compression. Ga-67 citrate study was mainly indicated in tumors with catecholamine depletion, which failed to concentrate the other two radiopharmaceuticals. I-131 MIBG proved especially useful in detecting neuroblastoma with negative Tc-99m MDP and Ga-67 citrate studies and also proved to be helpful with those cases in which I-131 MIBG was planned for therapy. The following strategy is suggested for evaluating neuroblastoma.(ABSTRACT TRUNCATED AT 250 WORDS)

3-Iodobenzylguanidine↗