bluuebunny/crossref_metadata_2025_split huggingface dataset:
Streptozotocin Resistance of the Genetically Diabetic KK Mouse
Authors: Iwatsuka Hisashi , Shino Ako , Taketomi Shigehisa 
Published: December 2014

Intraperitoneally administered streptozotocin (100 mg. per kilogram) produced hyperglycemia (higher than 200 mg. per 100 ml.) in 100 per cent of C57BL, but in none of KK mice. Pretreat-ment with phentolamine (50 mg. per kilogram), an α-adrenergic blocking agent, decreased resistance of KK mice to the diabetogenic action of streptozotocin. On the other hand, pre-treatment with propranolol (10 mg. per kilogram), a β-adrenergic blocking agent, induced resistance to streptozotocin in C57BL mice. This effect of propranolol was potentiated by administration of epinephrine (1 mg. per kilogram).
These findings suggest that the α-adrenergic system protects pancreatic β cells from cytotoxic action by streptozotocin, indicating a predominance of the α-adrenergic system in diabetic mice of the KK strain.
Inhibition of Pancreatic Glucagon Responses to Arginine by Somatostatin in Normal Man and in Insulin-Dependent Diabetics
Authors: Gerich John E , Lorenzi Mara , Schneider Victor , Kwan Chuk W , Karam John H , Guillemin Roger , Forsham Peter H 
Published: December 2014

Somatostatin, a recently synthesized hypothalamic peptide thought to represent growth hormone-release-inhibiting factor, has been previously shown to inhibit pancreatic glucagon secretion in species other than man. To determine whether somatostatin also inhibits human glucagon secretion, plasma glucagon responses during intravenous infusion of arginine alone (250 mg. per kilogram over twenty-five minutes) and in combination with synthetic cyclic somatostatin (20,μg. per minute) were compared in six normal and six insulin-dependent diabetic subjects.
Somatostatin abolished glucagon responses to arginine in both groups, with plasma glucagon declining transiently below basal levels; this occurred despite the fact that the diabetic subjects had fasting hyperglucagonemia and exaggerated glucagon responses during control arginine infusions. In both groups plasma glucose rises seen after arginine were diminished during somatostatin infusions, and, in the normal subjects, insulin responses were also inhibited.
These results demonstrate that somatostatin is a potent inhibitor of glucagon secretion in man. Accordingly, it may prove useful as an adjunct to insulin therapy in treatment of insulin-requiring diabetes mellitus.
Serum Enzyme Changes in Diabetic Ketoacidosis
Authors: Knight Anthony H , Williams David N , Spooner Richard J , Goldberg David M 
Published: December 2014

A study of thirty-six unselected episodes of diabetic ketoacidosis showed that multiple serum enzyme abnormalities, severe in degree, occurred in eleven (30.6 per cent). Seven could be explained wholly or partly by concurrent illness, such as myocardial infarction or gallstones, but no cause could be found in the other four cases. Since multiple enzyme abnormalities of lesser degree occurred without clinical explanation in a further three cases, the over-all incidence of multiple unexplained enzyme elevation was 19.4 per cent. A single serum enzyme activity was elevated over several consecutive samples during nine episodes: CPK was the enzyme concerned in three, and six were associated with abnormalities in enzymes specific for hepatobiliary disorders.
The prognosis is seriously affected by concurrent illness, but is not altered by the existence of enzyme abnormalities per se, no matter how severe; these may reflect transient leakage of enzymes from hepatocytes reversibly damaged by lysosomal constituents.
Basal Lamina Layering in Diabetes Mellitus: Evidence for Accelerated Rate of Cell Death and Cell Regeneration
Authors: Vracko Rudolf 
Published: December 2014

Excessive deposition of basal lamina in capillaries and othei structures of individuals with diabetes mellitus is characterized by formation of multiple layers of basal lamina and accumulation of cell debris between the layers. In capillaries with multiple BL layers, between pericytes and endothelial cells, only a single layer is generally present These and other features suggest that basal lamina formation is a quantified event and that excessive accumulation could be the result of (1) cell death and cell replacement, (2) discrete turning on and off of basal lamina production or (3) defective resorption of old basal lamina layers. Evidence indicating that the major component in the pathogenesis of basal lamina accumulation is cell death and cell regeneration is presented. Whether interrupted production or impaired resorption also contribute to this process is unknown.
The common presence of BL layering in patients with diabetes mellitus indicates that diabetics' cells are different from nondiabetics', the difference manifesting itself by increased rate of cell death. The focal nature of this process suggests further that injurious events in the cells' environment contribute to the pathogenesis of this lesion.
Whatever the cause, the BL characteristics discussed, like rings on cross-sections of tree trunks, give some indication of the number of cell generations which have occurred at that particular site.
Quantitative Study on the Potentiating Effect of Arginine on Glucose-induced Insulin Response in Healthy, Prediabetic, and Diabetic Subjects
Authors: Efendić Suad , Cerasi Erol , Luft Rolf 
Published: December 2014

Glucose dose-relations of the early and late insulin responses were established in control, prediabetic and mildly diabetic subjects by performing glucose infusions with varying doses in each subject. Our earlier demonstration that the dose-response curves for both the early and late insulin responses are shifted toward the high glucose region in prediabetes and diabetes was confirmed. In a second series of experiments, a thirty minute arginine infusion was given fifty minutes before the start of the glucose infusion. The insulin response to arginine was reduced in the prediabetics and diabetics. Plasma insulin returned to base line at the start of the glucose infusion in the controls and prediabetics, but not in the diabetics. The early insulin response to glucose infusion was markedly enhanced by pretreatment with arginine at all glucose doses used, both in the controls and the prediabetics, whereas the late response was not modified. The results in the patients with mild diabetes were not conclusive. In the controls and prediabetics, the glucose-insulin dose-response curves for the early response were steeper after pretreatment with arginine. The percentile increase in insulin response was fairly constant throughout the range of hypergly-cemia induced. The insulinogenic index was increased by arginine with a factor of around 2 in controls as well as prediabetics, regardless of the dose of glucose administered.
These results, together with data reported previously by our group, indicate that arginine acts on insulin secretion by magnifying, at a constant rate, the insulinogenic signal of glucose. In prediabetics (and probably also in persons with slight diabetes), in whom the insulinogenic signal of glucose on the β-cell is diminished, arginine exerts quantitatively a similar degree of amplification. Therefore, it seems reasonable to assume that the mechanisms which mediate the amplifying effect of arginine in the β-cell are not deranged in prediabetes.
Diabetes in Remission: Insulin Secretory Dynamics
Authors: Park Byung N , Soeldner J S , Gleason R E 
Published: December 2014

Insulin secretory capacity and sensitivity to exogenous insulin were examined in eight nonobese, ketosis-prone young diabetics at the time of a clinical remission during which they could be managed without any insulin therapy.
The insulin secretory capacity of these patients was assessed with oral glucose, intravenous glucose and an oral mixed meal test. The insulin responses were variable and relatively subnormal compared to those in normal controls, but definite and substantial responses were found in the majority of the patients to all the stimuli.
When small amounts of crystalline insulin were administered intravenously to produce peripheral venous insulin levels in the physiologic range, these patients responded with a normal decrease in blood glucose and plasma free fatty acid levels suggesting maintenance of in vivo insulin sensitivity.
Since ketosis-prone, insulin-dependent diabetics are generally characterized by nearly complete failure of beta-cell function, the present finding supports the concept that clinical remission of diabetes is dependent on a functional recovery of the beta cell. Furthermore, it seems likely that no significant “insulin resistance” that often accompanies severe diabetes is present in this remission state.
Oral Glucose-stimulated Insulin Release in Nondiabetic Twin Siblings of Diabetic Twins
Authors: Gottlieb Marise S , Soeldner J Stuart , Kyner Joseph L , Gleason Ray E 
Published: December 2014

A total of twenty-five monozygotic and dizygotic glucose-tolerant twin siblings of diabetic patients were compared with age-, sex-, and weight-matched groups of glucose-tolerant offspring of two diabetic parents and normal control subjects with regard to glucose, insulin, free fatty acid and growth hormone responses during a five hour oral glucose tolerance test. Few differences in mean levels of glucose, insulin or free fatty acids were found, the trend being a higher insulin level in the twin study groups. Although the numbers of subjects were small, significantly higher insulinglucose relationships were found in monozygotic females compared to normals and in dizygotic females compared to offspring and to normals. The fasting plasma free fatty acid level was highest in the twins among each of the four subgroups, possibly indicating a blunting of the antilipolytic effect of the basal insulin level in the twins.
A “paradoxic” type of growth hormone response was seen in both the twin and offspring groups compared to the respective normal groups.
It appears that alterations in insulin-glucose relationships and growth hormone response exist in potential diabetic groups that cannot be accounted for by small but important differences in age, weight, or glucose tolerance.
Placental Transfer of Streptozotocin in the Rhesus Monkey
Authors: Reynolds W Ann , Chez Ronald A , Bhuyan Bijoy K , Neil G L 
Published: December 2014

The induction of a diabetic-like state by the drug streptozotocin (Stz) has been useful for studies on the effects of maternal glucose intolerance upon the monkey fetus. However, the question of transplacental passage of Stz and its effect upon the fetus has to be considered if the drug is to be administered post-conception. Experiments in which Stz was administered maternally and then analyzed in maternal and fetal blood by disc-plate assay indicated prompt movement to the fetal circulation. Slow maternal degradation of Stz was associated with higher fetal blood levels of the compound.
Studies with 14C-streptozotocin suggest that about one half of the radioactivity present in maternal and fetal plasma following intravenous maternal administration is intact 14C-Stz; after one hour, only one fifth of the radioactivity is still associated with the Stz molecule. By the time maximum fetal levels of the drug were achieved, maternal levels of Stz had decreased to one sixth and one tenth of initial levels. Fetal levels did not exceed one half to one third of the simultaneous maternal plasma concentration, implying placental limitation to transfer of streptozotocin from mother to fetus.
No specific localization of 14C-Stz by pancreatic beta cells was observed in either paraffin or frozen-dried autoradiographic preparations. No evidence of high levels of uptake of 14C-Stz were found in pancreatic tissue in comparison to other selected fetal tissues.
Although Stz does cross the hemochorial placenta to a limited extent, it appears to have no discernible effect upon the fetal pancreas.
A Six-minute Test with Glucagon-free Insulin in the Classification of Diabetes and Prediabetes
Authors: Anderson George E 
Published: December 2014

Somogyi pointed out that conventional tests for insulin tolerance are not adequate for determining sensitivity or responsiveness to insulin, since blood glucose below the fasting level rapidly initiates counter-regulatory mechanisms which promptly mask the degree of response to insulin.
The uncertainty of the period of action of the hyperglycemic factor existing in presently available crystalline insulin makes it quite impossible to appraise satisfactorily the primary influence of the administered insulin on blood glucose in respect to the promptness of initiation of action (“latent period” of Himsworth) and in respect to the unhampered degree of fall in blood glucose. It is essential, therefore, that for a good test of responsiveness these latter two factors be registered before any extensive fall in glucose has had an opportunity to excite the body's counter-effort at homeostatic readjustment. Such time would fall well within the first few minutes after injection of insulin.
The valid criticisms of tests now in vogue for sensitivity to insulin can be obviated by careful timing, using an insulin which is free of the hyperglycemic-glycogenolytic factor (HGF or glucagon). The suggested responsiveness test with glucagon-free insulin records blood glucose readings in a time period before marked reactive compensatory phenomena have come into play, namely within the first six minutes after administration of the insulin. Under such conditions, only factors already residing in the individual and actively functioning at the very time of the injection of insulin could prevent the initiation of a fall in blood glucose. These are antiinsulin factors peculiarly inherent in the individual and possibly actually creating the diabetic state in the obese adult.
Metabolism of the Serum Lipids in Diabetes and in Arteriosclerosis
Authors: Mann George V 
Published: December 2014

As an experimentalist interested in arteriosclerosis, I look upon diabetes mellitus as a natural experiment in atherogenesis. This narrow view may distress clinicians engaged in the management or prevention of diabetes, but they should agree that progress in the prevention of atherosclerosis will benefit diabetic human beings most of all.
In 1947 I began a laboratory study of the effect of experimental diabetes on the development of vascular disease in animals. The premise that the presence of diabetes aggravates the vascular disease is so attractive that even after five years of fruitless work it is sometimes tempting to try again. It was not possible to demonstrate that this was a valid hypothesis. Although certain capillary lesions were demonstrated in diabetic rats, no evidences of major vessel disease were produced in either rats, dogs, or monkeys, whether fed cholesterol or not.
A second hypothesis concerning atherogenesis has been studied and contested for almost half a century and yet has eluded the critical experiment which will properly evaluate its verity. In simple terms this hypothesis states that atherosclerosis, a variant of arteriosclerosis, is a consequence of abnormal lipid metabolism. The immediate problems posed are those of describing the kind and extent of abnormal lipid metabolism necessary for this consequence, a description of the contribution or weight of abnormal lipid metabolism in this effect, and finally a description of the mechanism by which the lipid abnormality develops. There is now a great deal of acceptable information on these points, but for the present I shall consider some evidence that my associates and I have obtained in studies of diabetic human subjects. If from the relation of these observations, any suggestions or implications are made for the management of diabetes, they are fortuitous.
The Young Diabetic Panel Discussion
Authors: White Priscilla , Guest George M , Harwood Reed , Kennedy William B 
Published: December 2014

Moderator White: The most important age periods in the management of the juvenile diabetic patient are infancy and adolescence. Some physicians dread the management of diabetes when the patient is under five years of age. The condition sometimes seems difficult to handle and it places extreme strain on the morale of the patients. Dr. Guest, what is your advice in regard to the diabetic infant?
Dr. Guest: In my opinion diabetic infants are not necessarily more difficult to manage than older children. I should say that the age of adolescence is a much more difficult period than that of infancy, but then of course, other problems are involved. As most of you know, I recommend the so-called “free-diet-glycosuric” regime which is a subject of continuing debate. (See editorials in Diabetes: 1:487–89, Nov.-Dec. 1952.) In our clinic we have eighteen diabetic infants with onset of diabetes under the age of two years. Of these, eight were under one year of age when symptoms were first recognized. The youngest started glycosuria at nine days of age. The diagnosis was made by the astute mother because she had another diabetic child then aged one and onehalf years. When she noted the new infant was passing a lot of urine, she tested it and found sugar. On admission to the hospital, the baby's blood sugar was 350 mg. per 100 cc. The urinalysis showed 3-plus glycosuria but no ketonuria. During twenty-four hours we determined the blood sugar every two hours and found it fluctuating between 300 and 500. Because there was no ketonuria, we felt that a period of observation before starting insulin would do no harm. After that brief period of observation the baby was given an initial dose of three units of protamine zinc insulin. During the next twenty-four hours the blood sugar fell progressively (determined at two-hour intervals) to 150 and then 100. Again, three units of protamine zinc insulin kept the blood sugar within normal range. (Let me stress the necessity for microchemical methods for following blood chemical changes in infants, whether diabetic or nondiabetic.) The baby was sent home on the fifth day, receiving two units of protamine zinc insulin daily. He was breast fed for ten months, on a demand schedule, with the dosage of protamine zinc varying from one to three units daily and solid foods offered at usual ages. (Please note that breast feeding is the ultimate in “free diet”, while it lasts!) That child is now seven years of age and has not suffered any illness that required hospitalization. His urine is rarely free of sugar, but excessive glycosuria with polyuria is likewise rare. Transient ketonuria has occurred occasionally during intercurrent infections, but has always cleared up promptly with the administration of extra doses of quick-acting insulin. The insulin requirement increased slowly with age and increasing body weight, from five units a day at one year of age, to thirty-five units (globin insulin) a day at the present time.
Workshop Report: Treating Diabetes and its Complications
Authors: Fajans Stefan S , Nutting Paul 
Published: December 2014

RESEARCH OPPORTUNITIES— The work group discussed research opportunities in biomedical, behavioral, and health service research on some of the complications of NIDDM. The panel chose to focus on aspects of the prevention of blindness, nephropathy, heart disease, and amputations, and aspects of gestational diabetes and diabetes in pregnancy.
The panel agreed at the onset that the best treatment of diabetes and its complications was prevention of diabetes by treating early abnormalities of glucose tolerance or impaired glucose tolerance. Primary prevention of diabetes may be achieved by treating such abnormalities by diet, exercise, or oral hypoglycemic agents. Alternatively, treatment of the earliest abnormalities of NIDDM, such as a diabetic glucose tolerance test, early in the natural history of diabetes might also be effective. These topics were discussed in more detail in the work group on the Prevention and Early Treatment of NIDDM.
Neurophysiological Evidence for Altered Higher Brain Functions in NIDDM
Authors: Kurita Akira , Katayama Ko , Mochio Soichiro 
Published: December 2014

OBJECTIVE
To investigate neurophysiological alterations of higher brain function in patients with NIDDM.

RESEARCH DESIGN AND METHODS
Auditory P300 event-related potentials were recorded in 60 NIDDM patients who had no evidence of stroke, dementia, or any other neurological illnesses. The P300 wave latencies in diabetic patients were compared with those in neurologically healthy control subjects, with consideration of clinical parameters and diabetic complications.

RESULTS
Diabetic patients had significantly longer P300 latencies than control subjects. Seven diabetic patients had pathologically prolonged P300 values. There was a trend toward longer P300 latencies in diabetic patients with retinopathy and in those with HbA1 of ≥10%; the differences between these diabetic subgroups and control subjects were both statistically significant. However, three of seven diabetic patients with abnormal P300 latencies had no retinal lesions, and no significant correlation was observed among diabetic patients between P300 latencies and HbA1 levels. Peripheral neuropathy, nephropathy, blood glucose levels, and disease duration appeared not to correlate with P300 alterations.

CONCLUSIONS
These findings suggest the presence of central nervous pathological processes in NIDDM that affect higher brain functions, as assessed by P300 latencies. Our findings also suggest that microangiopathy and metabolic derangement during the preceding 4- to 8-week period may contribute in small part to the pathophysiology of this central nervous involvement.
A single dose vaccination with an elastase-dependent H1N1 live attenuated swine influenza virus protects pigs from challenge with 2009 pandemic H1N1 virus
Authors: Mašić Aleksandar , Woldeab Niziti , Embury-Hyatt Carissa , Zhou Yan , Babiuk Shawn 
Published: December 2014

Abstract
The 2009 outbreak of H1N1 influenza A viruses in humans underscored the importance of pigs in influenza A virus evolution and the emergence of novel viruses with pandemic potential. In addition, influenza A virus infections continued to cause production losses in the agricultural industry resulting in a significant drop of profit. The primary method to control influenza A virus infections in pigs is through vaccination. Previously we demonstrated that two doses of an elastase-dependent live attenuated swine influenza virus administered by either the intratracheal or intranasal route can provide a high degree of protection in pigs against challenge with both homologous and different heterologous swine influenza viruses. Here we report the protection efficacy of a single dose elastase-dependent live attenuated swine influenza virus administered by the intranasal route against challenge with homologous subtypic H1N1 2009 pandemic swine-like influenza virus. Protection was observed in the absence of neutralizing antibodies specific for H1N1 2009 in sera.
A Transformer Class E Amplifier
Authors: Mikolajewski Miroslaw 
Published: December 2014

Abstract
In a high-efficiency Class E ZVS resonant amplifier a matching and isolation transformer can replace some or even all inductive components of the amplifier thus simplifying the circuit and reducing its cost. In the paper a theoretical analysis, a design example and its experimental verification for a transformer Class E amplifier are presented. In the experimental amplifier with a transformer as the only inductive component in the circuit high efficiency ηMAX = 0.95 was achieved for supply voltage VI = 36 V, maximum output power POMAX = 100 W and the switching frequency f = 300 kHz. Measured parameters and waveforms showed a good agreement with theoretical predictions. Moreover, the relative bandwidth of the switching frequency was only 19% to obtain output power control from 4.8 W to POMAX with efficiency not less than 0.9 in the regulation range.