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Biomedical subjects

W A Bauman

Publications and source records attributed to W A Bauman.

At least 19 recordsLinked to original sources

Cholecystokinin upregulation during intestinal repair.

To determine whether cholecystokinin (CCK), a small intestinal hormone, may have autocrine or paracrine functions, gene regulation in the rat stomach and duodenum has been evaluated following cytotoxic injury. We quantified total RNA, CCK messenger RNA (mRNA), total protein, small and large forms of CCK peptides and gastrin. The stomach and the intestine respond differently. Following cytotoxic injury duodenal total RNA falls (1.5 +/- 0.1 vs 0.18 +/- 0.04 mg/g P less than or equal to 0.0001), and CCK mRNA content is depleted (260 +/- 23 vs 41 +/- 8 pg CCK mRNA/duodenum P less than or equal to 0.0001), yet there is a paradoxical increase in CCK mRNA concentration (176 +/- 20 vs 303 +/- 38 pg CCK mRNA/mg total RNA P less than or equal to 0.01). Increases occurred in both molecular species of CCK peptides evaluated: CCK8 (8 +/- 7 vs 26 +/- 2 pmole/g P less than or equal to 0.0001), large forms of CCK (42 +/- 4 vs 250 +/- 27 pmole/g P less than or equal to 0.0001). By contrast, in the stomach, only decreases were observed. These data identify sites of anatomical and biosynthetic upregulation during gastrointestinal repair. Changes are dependent upon the length of the period of recovery, differ between stomach and duodenum, and may be age related. Intestinal CCK may have para- and or autocrine roles in addition to its hormone function.

Animals

Depressed serum high density lipoprotein cholesterol levels in veterans with spinal cord injury.

Cardiovascular diseases are the most frequent cause of death among persons with spinal cord injury (SCI), and these diseases are reported to occur prematurely in the disabled compared to the able bodied population. The mechanism of accelerated coronary heart disease (CHD) in persons with SCI may be partially explicable on the basis of the lipoprotein profile. We performed fasting lipoprotein determinations on 100 veterans with SCI, 50 with paraplegia and 50 with quadriplegia, and 50 veteran controls. The mean age of the subjects with SCI was 47.8 +/- 1.4 years with a duration of injury of 16.3 +/- 1.2 years. The mean serum high-density lipoprotein (HDL) cholesterol was depressed in subjects with paraplegia or quadriplegia compared to controls (37 +/- 1 or 40 +/- 1 versus 48 +/- 2 mg/dL, p < 0.0001). Although serum total cholesterol was lower (p < 0.01) in subjects with SCI than in controls, there was no significant difference in mean serum low-density lipoprotein (LDL) cholesterol. Thirty-seven percent of subjects with SCI have serum HDL cholesterol levels less than 35 mg/dL with no significant difference in lipoprotein distribution between high and low cord lesions. Eighteen percent of individuals with SCI have an absolute elevation of LDL cholesterol (greater than 160 mg/dL). About 40% of those with SCI and LDL cholesterol levels between 130 and 160 mg/dL also have serum HDL cholesterol values below 35 mg/dL, all of whom would have their serum HDL cholesterol level undetected if lipoprotein profiles were performed according to present recommendations--that is, only if the serum total cholesterol is elevated.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

The serum lipoprotein profile in veterans with paraplegia: the relationship to nutritional factors and body mass index.

Individuals with spinal cord injury have a shortened life expectancy, with coronary heart disease as a leading cause of death. Identifying potentially reversible risk factors would be expected to be of value in the long-term care of the person with a spinal cord injury. We addressed the relationships among diet, body mass index, and serum lipid levels in 28 veterans with paraplegia compared to 52 age-matched ambulatory veteran controls. There are no significant differences in body mass index or in total caloric, saturated fat, or cholesterol intake between those with paraplegia and the control group. The serum HDL cholesterol level is significantly lower in those with paraplegia compared to the control group (35 +/- 2 vs 49 +/- 2 mg/dL). There are no significant differences noted in serum total cholesterol, LDL cholesterol, or triglycerides between the groups. Total caloric intake decreases significantly with age in the control subjects but not in the subjects with paraplegia. Inverse correlations are found between serum HDL cholesterol and serum triglycerides levels both in those with paraplegia (r = -0.54, p less than 0.005) and in the controls (r = -0.42, p less than 0.001). In our group of subjects with paraplegia, serum lipid levels appear to be independent of dietary intake and body weight.

Adult

Drug use and abuse in an urban veteran spinal cord injured population.

Substance abuse in the spinal cord injured (SCI) population has been addressed in a few controlled studies. These reports have led to the belief that many SCI patients were illicit drug users prior to their injury and that their drug abuse was a contributing cause of their accidents. One large study determined from answers obtained on a questionnaire that drug abuse, other than alcohol, was prevalent among injured veterans. Our study uses urine toxicology to determine the frequency of drug use and abuse, excluding alcohol, in 72 inpatients and 81 outpatients associated with an urban Veterans Affairs Medical Center. In a blinded experiment, urinary concentrations of opiates, barbiturates, amphetamines, methadone, benzodiazepines, and cocaine were determined with Syva reagents on an Abbott VP. Urinary cannabinoids were determined using Abbott TDX and the FPIA method. The use of illicit (unprescribed) drugs was surprisingly low (< or = 13 percent) for an urban medical center. Outpatient cannabinoid abuse was significantly more frequent than inpatient usage (p < 0.01). Barbiturates were not found in any patient. Benzodiazepines were taken most commonly (29 percent). Since benzodiazepine usage is the direct result of physician prescription, wide-spread usage of this agent is avoidable. Physicians should pay attention to the probable deleterious consequences of benzodiazepine addiction related to depressive effects on the central nervous system caused by its chronic use.

Adult

Coronary artery disease: metabolic risk factors and latent disease in individuals with paraplegia.

Individuals with spinal cord injury (SCI) currently have a longer life span as a result of recent improvements in medical care. As in the able-bodied population, cardiovascular disease is the leading cause of death in persons with SCI, but it appears to occur at younger ages in those with SCI than in the able-bodied population. The reduction in level of activity and adverse changes in body composition caused by SCI have profound metabolic consequences that may influence the progression and severity of coronary artery disease. Metabolic sequelae of SCI include disorders of carbohydrate and lipid metabolism. Almost half of the 45 active, healthy subjects with paraplegia we studied have a disorder of carbohydrate tolerance, 1 in 5 subjects having a diabetic oral glucose tolerance test. Hyperinsulinemia is found in those with abnormal glucose tolerance. Subjects with paraplegia having impaired glucose tolerance or diabetes mellitus are significantly older than those with normal glucose tolerance. High-density lipoprotein cholesterol is markedly depressed, and low density lipoprotein is relatively elevated. Radionuclide myocardial perfusion imaging after upper body ergometry exercise reveals latent coronary artery disease in 12 of 19 subjects with paraplegia.

Adult

Is aging preprogrammed? Observations from the brain/gut axis.

Age related differential gene expression occurs in the neuro-enteral axis. Brain and gut organ weight, total RNA, total protein and three peptides were quantified in 4-, 10- and 37-week-old Sprague-Dawley rats. As animals aged, total RNA decreased in the brain (0.65 +/- 0.3-0.28 +/- 0.03 mg/g), but remained stable in the gut (2.6 +/- 0.3-2.9 +/- 0.4 mg/g). Total protein concentration rose in the duodenum (612 +/- 28-734 +/- 34 mg/g), while levels remained stable in the brain (641 +/- 54-666 +/- 34 mg/g). Three peptides were studied, cholecystokinin (CCK), VIP and secretin. With increasing age, significant changes were found only in CCK a true neural-enteral peptide. The concentration of smaller molecular forms of CCK decreased in the brain (248 +/- 18-188 +/- 21 pmol/g), while they remained stable in the duodenum (33 +/- 2-36 +/- 3 pmol/g). By contrast, the concentration of the larger forms of CCK were stable in the brain (36 +/- 3-40 +/- 4 pmol/g), but rose in the gut (89 +/- 14-134 +/- 17 pmol/g). These data indicate that as rats age there is preprogrammed differential control of gene expression between brain and intestine.

Aging

Seasonal changes in pancreatic insulin and glucagon in the little brown bat (Myotis lucifugus).

Seasonal changes in pancreatic insulin and glucagon were investigated in the little brown bat (Myotis lucifugus). Pancreatic protein content increased 21% from the nonhibernating state in June compared to the nonhibernating or early hibernating state in late October, and then decreased 50% between October and the months of deep hibernation. The content of insulin and glucagon increased from June to October, and both hormones further increased during hibernation, when a fall in pancreatic protein content occurred. The concentration of both insulin and glucagon increased from October to February. Of note, the insulin concentration progressively increased during deep hibernation from February to April, whereas the glucagon concentration remained constantly elevated throughout this time interval. The persistent elevation of pancreatic glucagon during hibernation may be related to its role in counterregulation and carbohydrate homeostasis during fasting. The elevation of pancreatic insulin, and its further increase during hibernation, is less clear but may be hypothesized to provide a rapidly releasable storage pool required for immediate secretion during arousal, possibly to prevent a hyperosmolar state.

Analysis of Variance

Cerebral cortical concentrations of bioamines and their metabolites during arousal and after feeding in the little brown bat (Myotis lucifugus).

The concentrations of bioamines and their metabolites have been determined in March and April during arousal from hibernation in the cerebral cortex of the little brown bat (Myotis lucifugus). The patterns during arousal for dopamine and serotonin (5-HT) were similar with a significant fall in concentrations by 1 h of arousal, and an inverse relationship with their respective metabolites, 3,4-dihydroxyphenylacetic acid and 5-hydroxyindolacetic acid (5-HIAA). This suggests an acute release and metabolism of these bioamines with onset of arousal. During arousal, cerebral cortical concentrations of norepinephrine (NE) were not significantly changed. Levels of homovanillic acid were markedly depressed during hibernation and rose acutely with arousal. After arousal and 4 days of feeding in April, there was an increase in all bioamines and their metabolites studied except for NE. Of note is the marked decrease in the hibernating level of 5-HT and increase in its metabolite 5-HIAA from March to April, which may herald the natural termination of hibernation. Our results suggest that the brain of hibernators undergoes complex changes in the modulation of neurotransmitter systems which are consistent with both down- and up-regulation of neuronal activity in the maintenance of hibernation and the initiation of the arousal process.

Animals

Hyperinsulinemia.

Patients with mild or early non-insulin-dependent diabetes mellitus often display a delay in insulin response followed by late hyperinsulinemia during oral glucose tolerance testing. Those patients with long-standing disease or elevations of fasting plasma glucose in excess of 140 mg/dl are generally hypoinsulinemic in response to an oral glucose tolerance test. Diabetic patients who do not have an acute response to intravenous glucose may have normal responses to intravenous tolbutamide or intravenous arginine, suggesting that delayed responsiveness to glucose is not due to decreased pancreatic insulin content. An association between hyperinsulinemia and hypertension has been suggested by recent studies from several laboratories. In a homogeneous population of men who suffered traumatic bilateral above-the-knee amputation in the Vietnam War with subsequent development of obesity, it was shown that there was strong correlation between hypertension and hyperinsulinemia during oral glucose tolerance testing despite only mild glucose intolerance. In addition, a subset of hypertensive women who were in their third trimester of pregnancy were markedly hyperinsulinemic during oral glucose tolerance testing in the absence of any abnormalities of glucose tolerance. Thus, the relationship between hyperinsulinemia and hypertension, and the possible reasons for this relationship, are fields of active investigation at present.

Acute Disease

Early and long-term effects of acute caloric deprivation in obese diabetic patients.

PURPOSE: It is generally assumed that diet therapy can ameliorate the metabolic derangements experienced by obese type 2 diabetic patients, thereby leading to discontinuation of insulin or oral sulfonylurea drug therapy. We decided to retrospectively investigate which clinical and biochemical parameters affect therapeutic responses. PATIENTS AND METHODS: Sixty-four poorly controlled obese diabetic patients were hospitalized and placed on a precisely defined, hypocaloric diet. Known duration of diabetes, type of pharmacologic therapy, body weight, weight loss, fasting plasma glucose concentrations, C-peptide levels, hemoglobin A1C, and plasma lipid levels were assessed, as were nitrogen and electrolyte balances. RESULTS: Average weight loss was 13 pounds in a mean of 23 days. During hospitalization, the mean fasting plasma glucose value for the group fell from 221 +/- 10 to 122 +/- 5 mg/dl. In 45 patients (73 percent), the final fasting plasma glucose level was less than 125 mg/dl (mean: 102 +/- 2 mg/dl). Oral glucose tolerance even in those patients in whom fasting plasma glucose levels normalized was still grossly diabetic at the end of the hospital stay, deteriorating further after three days of liberalized caloric intake. In part this may have been due to decreased insulin secretory reserve as reflected by blunted plasma C-peptide response. Forty of 42 patients who entered the study taking insulin were able to discontinue the drug within one to seven days of hospitalization. After a mean follow-up period of 19 months, only 10 of 50 patients continued to maintain fasting euglycemia; five were on diet alone, and five were receiving oral hypoglycemic agents. Thirteen patients were receiving insulin therapy. CONCLUSION: Diet therapy in these patients resulted in short-term improvement of glycemic control and, in the majority, normalization of fasting plasma glucose levels. However, long-term outpatient follow-up revealed that relapse occurred in most patients.

Blood Glucose

Cholecystokinin (CCK) and vasoactive intestinal peptide (VIP) in the cerebral cortex of the non-hibernating and hibernating golden mantled ground squirrel.

1. The effect of hibernation on cerebral cortical concentrations of cholecystokinin and vasoactive intestinal peptide was investigated in the golden mantled ground squirrel (Citellus lateralis). 2. During hibernation, cortical brain weight decreased to 83% of the non-hibernating weight. 3. The concentration of the small form of CCK was significantly reduced. The concentration of the large forms of immunoreactive CCK did not significantly change during hibernation. The molecular forms of CCK appeared the same both before and during hibernation. 4. Of note, the concentration of vasoactive intestinal peptide significantly increased during hibernation. 5. Since there was a three-fold reduction in the ratio of large to small forms of CCK during hibernation, this suggests that post-translational processing of the precursor peptides are markedly reduced during hibernation.

Animals

An association between hyperinsulinemia and hypertension during the third trimester of pregnancy.

We studied 43 women in their third trimester of pregnancy whose fetuses were at significant risk of intrauterine growth retardation. To define metabolic subtypes for intrauterine growth retardation, a 100 gm glucose load was administered after an overnight fast. Twenty-seven women were normotensive and 16 had hypertension. The glucose tolerance of the hypertensive group was essentially the same as that of the normotensive group. However, 8 of the 16 women with hypertension had marked hyperinsulinemia in response to an oral glucose load. Of the five women with hypertension who gave birth to offspring of low birth weight, three had hyperinsulinemia.

Blood Glucose

Factitious hyperinsulinemic hypoglycemia: confirmation of the diagnosis by a species-specific insulin radioimmunoassay.

Surreptitious self-administration of insulin is an important cause of hypoglycemia. A 28-year-old female hospital ward clerk presented with hypoglycemia associated with an elevated plasma insulin level and a low plasma C-peptide concentration. Factitious illness was denied by the patient until it was definitively proven by using a species-specific insulin radioimmunoassay that the type of insulin circulating at the time of hypoglycemia was of animal rather than of human origin. The differential diagnosis of hypoglycemia associated with hyperinsulinemia and the current laboratory methods which may be employed to distinguish between factitious hypoglycemia and endogenous hyperinsulinism are discussed.

Adult

Pancreatic hormones in the nonhibernating and hibernating golden mantled ground squirrel.

The effects of hibernation on pancreatic insulin, glucagon, somatostatin, and pancreatic polypeptide was investigated in the golden mantled ground squirrel (Citellus lateralis). During hibernation, pancreatic organ weight decreased to 57% of the nonhibernating weight. The content of all four pancreatic hormones during hibernation was significantly reduced. The concentrations of insulin, pancreatic polypeptide and somatostatin, but not of glucagon, were significantly reduced during hibernation. The maintenance of the pancreatic glucagon concentration during hibernation may be related to its role in counter-regulation and carbohydrate homeostasis during fasting.

Animals

A high molecular weight form of pancreatic polypeptide was present in USP insulin and is absent in a more recent insulin preparation.

The concentrations and molecular forms of pancreatic polypeptide (PP) and glucagon were determined in USP XX and single-peak insulin preparations. In USP insulin the concentration of PP was 7 ng mg-1 insulin; on gel chromatography the PP immunoreactivity fractionated into two peaks of about equal size. One of the PP peaks was in the region of 4200 dalton PP, and the other PP peak eluted earlier in the region of a 7000-10,000 dalton peptide. The concentration of PP in single-peak insulin was 0.8 ng mg-1 insulin; the immunoreactivity eluted in a single peak in the region of [125I]PP. The concentration of glucagon in each preparation was 55 ng mg-1 insulin. On gel chromatography the immunoreactive glucagon in each insulin preparation eluted in the region of [125I]glucagon.

Glucagon

Stimulation of human pancreatic polypeptide and gastrin by Boots and GIH secretin: in vitro and in vivo studies.

We have studied the concentration of various gastrointestinal peptides in a crude porcine secretin (Boots) preparation and pure natural porcine secretin (GIH, Kabi) preparation. Boots secretin was found to contain 140.3 ng secretin, 1.27 ng human pancreatic polypeptide (hPP), 1.03 ng gastrin, 137.4 ng cholecystokinin (CCK), 241 microU insulin, 1.86 ng vasoactive intestinal polypeptide (VIP), 2.22 ng glucagon and 6.60 ng somatostatin (SRIF) per Crick Harper unit Boots secretin. Sephadex gel filtration demonstrated that the immunoreactivity was due to the hormone per se. GIH secretin contained 240 ng secretin per clinical unit (CU) and less than detectable concentrations of hPP, gastrin, CCK, insulin, VIP, glucagon and SRIF. To determine the clinical significance of having contaminating peptides in Boots secretin, we investigated the effect(s) in 4 subjects. Determined in a highly gastrin-specific assay, the mean plasma gastrin response to Boots secretin administration was slightly, but not significantly greater than the GIH secretin response at 1 and 2.5 minutes. However, in some subjects false positive elevations in plasma gastrin immunoreactivity occurred when some commercially available kit gastrin assays were employed. After intravenous injection of Boots secretin, mean plasma hPP levels rose significantly more than after GIH secretin administration. The mean peak plasma insulin level after GIH secretin administration was significantly higher than after Boots secretin. Neither secretin preparation caused a change in plasma glucose, glucagon and SRIF levels. From these results, it is suggested that GIH secretin be used as the preparation of choice in provocative testing for diagnosing gastrinoma or deficiencies of exocrine pancreatic function.

Adult

Pancreatic A and B cell stimulation in euthermic and hibernating marmots (Marmota flaviventris): effects of glucose and arginine administration.

In euthermic and hibernating marmots (Marmota flaviventris), the pancreatic A and B cells respond in the appropriate secretory manner to glucose or arginine injection. Although reduced, this response, is clearly present in hibernating marmots. When glucose is administered to euthermic or hibernating marmots, plasma insulin concentrations rise and glucagon levels fall. While similar results are obtained in hibernation, the time period of the response is much longer due to the slowing of temperature dependent metabolic processes. Injection of L-arginine stimulates an increase in plasma glucose, insulin, and glucagon as expected. Measurements of plasma glucose, insulin, and glucagon under basal conditions, suggest that there are no significant differences between any phase of hibernation (eg. entrance, deep hibernation, arousal) and euthermia. These results provide indirect evidence that the pancreatic A and B cells of hibernating marmots continue to function in order to help regulate plasma glucose concentration.

Animals