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Biomedical subjects

C F Howard

Publications and source records attributed to C F Howard.

At least 19 recordsLinked to original sources
PubMed1990

Hyperinsulinemia in Macaca nigra: precession to obesity and/or diabetes?

A subset of Macaca nigra have been identified with elevated levels of fasting and secretory insulin. The insulin increment between 0 and 15 min in an intravenous glucose tolerance test (IV-GTT) was 511 +/- 42 microU/ml in hyperinsulinemic (HYPER) monkeys compared to 191 +/- 16 microU/ml in nondiabetic (ND) controls (p less than 0.01). Fasting insulin increased from 37 +/- 4 in ND to 57 +/- 7 microU/ml in HYPER monkeys (p = 0.02). Glucose clearance also increased from 3.87 +/- 0.18 in ND to 5.78 +/- 0.52%/min in HYPER monkeys (p less than 0.01). The acute (239 +/- 31 versus 137 +/- 19 microU/ml/min) and secondary insulin responses (542 +/- 75 versus 207 +/- 32 microU/ml/min) were significantly greater in the HYPER monkeys than in the ND controls, respectively (p less than 0.05). The rate of glucose clearance per amount of insulin secreted was diminished about 40% in both the acute and the secondary phases of HYPER monkeys (p less than 0.02). Total C-peptide secretion was two times greater in HYPER than in ND monkeys (p = 0.05). The HYPER monkeys averaged 12-20% greater weight and 41-44% greater body mass than the ND monkeys (p less than 0.05), although both groups were fed the same amount of diet and were well within nonobese limits. These Macaca nigra appear to have a functional lesion with excess insulin secretion, relatively impaired clearance of glucose, and possible insulin resistance, but no islet pathological lesion. Development toward overt diabetes might be exacerbated if obesity became a more dominant factor.

Animals↗
PubMed1990

Diabetes mellitus in nonhuman primates: recent research advances and current husbandry practices.

Primates can be utilized for a variety of studies to give insight into the mechanisms of the onset and progression of diabetes mellitus and obesity, and into the development of secondary manifestations. Results can be used to understand the etiologies and effects of diabetes in human beings. Investigators and animal care personnel should be continually aware of the potential for development of diabetes among primates and should seek to identify the earlier stages before the appearance of overt diabetes. In addition to updating recent research in which nonhuman primates have been used in studies on the different forms of diabetes, this review also furnishes some information about therapeutic management and husbandry of monkeys with predispositions toward diabetes or with overt diabetes.

Amyloidosis↗
PubMed1989

Abnormalities in insulin secretion and glucose clearance among Macaca mulatta examined on Cayo Santiago.

Macaca mulatta on Cayo Santiago (CS) were examined with intravenous glucose tolerance tests (IV-GTT) for evidence of abnormalities in glucose clearance and insulin secretion. About 10% of the 98 monkeys had impaired glucose clearance associated with impaired insulin secretion. Another 6% had either fasting or secretory hyperinsulinemia with slightly increased rates of glucose clearance, and 20% had low insulin secretion, but no significant changes in glucose clearance. Results were compared to those obtained with CS-derived monkeys tested at Sabana Seca (SS). Glucose clearance per amount of insulin secreted was 40% more effective among CS macaques than among those at SS. There were no differences in weight between impaired and control macaques on CS. Effects of genetics, physical activity, and food consumption can be studied among these macaques and results related to similar metabolic abnormalities in prediabetic and diabetic human beings.

Academies and Institutes↗
PubMed1988

Reaction patterns of islet-cell autoantibodies in Macaca nigra.

Circulating islet-cell autoantibodies (ICAAs) that reacted specifically with cytoplasmic components have been found in the blood of prediabetic Macaca nigra. The three distinct reaction patterns observed involved the majority of islet cells throughout the islet; a moderate number of cells, mainly at the islet periphery and around the vasculature; and a few cells scattered throughout the islet. Pancreas sections incubated with sera containing ICAAs followed with peroxidase-conjugated antibody were then reacted with anti-insulin, antiglucagon, or antisomatostatin antisera. The pattern associated with most of the islet cells was shown to be reactive to beta cells and was termed B-ICAA; the pattern with cells at the periphery was identified as alpha cells (A-ICAA); and the scattered cells contained somatostatin (D-ICAA). None of the three islet hormones were able to block ICAA reaction after overnight incubation, so the ICAAs are not anti-islet hormone antibodies. The varied reactions with antigens of different secretory cells indicate release of a variety of immunogens from islet cells as they necrose and cause the formation of different ICAAs.

Animals↗
PubMed1988

Comparison of glucose and insulin concentrations in macaque sera and plasma.

The glucose and insulin concentrations in blood from Macaca nigra and M. mulatta were determined after an overnight fast and 3 min after a glucose infusion. Blood treatment included clotting for serum or additions of fluoride, heparin, or heparin plus fluoride. Samples were centrifuged at 0 min or after being held at 22 degrees C for 20, 40, or 60 min. Levels of glucose and insulin generally agreed within 1 SD at all times examined for samples removed at 0 or 3 min.

Animals↗
PubMed1987

Lipoprotein patterns in nondiabetic, borderline diabetic, and diabetic Macaca nigra.

Lipoproteins were isolated by sequential ultracentrifugation, and the concentrations and compositions were determined in nondiabetic (ND), borderline diabetic (BD), and diabetic (D) Macaca nigra males consuming a chow ration. The total concentrations and components of the VLDL and IDL increased significantly with metabolic deterioration (P less than 0.01). Concentrations and components of LDL increased in the BD and D monkeys, but changes were not statistically significant. The HDL2 and HDL3 particles were virtually unchanged among the three different metabolic groups. The VLDL was the major carrier of the triglycerides, especially in D monkeys. Cholesterol was present predominantly in the LDL. The LDL-cholesterol to HDL-cholesterol ratio increased in the BD and D monkeys, owing mainly to increases in the LDL-cholesterol content. Apoprotein antisera showed apoprotein B in the VLDL, IDL, and LDL, apoprotein E in the VLDL and IDL, and apoprotein A-I in the HDL2 and HDL3 fractions. Because Macaca nigra consume a nonatherogenic, low-cholesterol, low-fat ration, the changes in lipoproteins, particularly in VLDL and IDL, are attributable to metabolic alterations associated with diabetes.

Animals↗
PubMed1986

Potentiation with epinephrine of macaque platelet aggregation by other agonists: implications for studies on human atherosclerosis.

The effects of low concentrations of epinephrine on the aggregation of macaque and human platelets by arachidonic acid (AA), collagen, and thrombin were studied. When epinephrine (0.05 to 1 microM) was added to macaque or human citrated or macaque heparinized platelets, either before or after the addition of near-threshold concentrations of AA, significant increases in aggregability were always seen. Epinephrine alone did not aggregate macaque platelets from citrated blood. When near-threshold concentrations of collagen or thrombin were present in the medium, low concentrations of epinephrine (0.05 to 0.50 microM) potentiated the aggregation of macaque and human citrated platelets and macaque heparinized platelets. The P values for the addition of epinephrine were less than 0.01 in all series. The ability of low epinephrine concentrations to potentiate aggregation of macaque platelets by other agonists is of particular significance because in humans the most important effect of epinephrine on platelets in vivo is probably the potentiation, by low concentrations, of aggregation induced by other aggregatory agents normally present in the blood in low concentrations.

Animals↗
PubMed1986

Longitudinal studies on the development of diabetes in individual Macaca nigra.

Development of spontaneous diabetes has been monitored in individual Macaca nigra. In this study, pancreatic biopsies were taken, islets were assessed morphologically, and results were related to the metabolic/clinical status. A biopsy or autopsy sample was obtained 4 to 10 years later, and the islet morphological state was again related to the metabolic/clinical status. Metabolic deterioration was correlated to the islet lesion, in which there was gradual loss of islet secretory cells and concurrent amyloid deposition. As nondiabetic monkeys with 0 to 3% islet amyloid progressed up to 20 to 40% amyloid, the insulin secretion and glucose clearance were both decreased (p less than or equal to 0.01), and the glucose and glucagon levels increased (p = 0.05). Impaired monkeys progressed to overt diabetes when islet amyloid exceeded 50 to 60%. Diabetic monkeys developed hyperglycaemia, along with impaired insulin secretion and glucose clearance (p less than 0.01). Loss of islet cells results in metabolic deterioration. The lesion precedes development of overt diabetes in Macaca nigra.

Amyloid↗
PubMed1986

Effects of ADP and epinephrine on macaque and human platelets. Implications for studies on human atherosclerosis.

The ranges for near-threshold ADP concentrations for the aggregation of macaque and human citrated platelets overlapped. The minimum concentrations of epinephrine, 0.05 microM to 1.0 microM, that at least doubled the aggregation response at threshold ADP concentrations were comparable for macaque and human citrated platelets. Epinephrine (1.0 microM to 10 mM) alone never aggregated macaque citrated platelets. Biphasic aggregation occurred with both macaque and human citrated platelets. The addition of heparin to a final concentration of 2.2 units/ml had no effect on the threshold ADP concentrations or the sensitivity of macaque or human citrated platelets to epinephrine. One microM phentolamine eliminated the potentiating effect of 1 microM epinephrine on ADP-induced aggregation of macaque and human citrated platelets. The threshold concentrations of ADP for macaque platelets were sharply reduced when heparin was used as an anticoagulant rather than citrate. However, epinephrine induced a similar increase in aggregability with both citrated and heparinized platelets, 0.55 +/- 0.09 SEM% and 0.44 +/- 0.09 SEM%, respectively. These data indicate that macaque and human platelets behave in a similar manner in response to ADP and that epinephrine potentiates the ADP-induced aggregation of macaque and human platelets equally well.

Adenosine Diphosphate↗
PubMed1986

Transmission of simian acquired immunodeficiency syndrome with a type D retrovirus: immunological aspects.

Simian acquired immunodeficiency syndrome (SAIDS) was transmitted to four of four rhesus macaques with blood from rhesus macaques naturally infected with a type D retrovirus, simian retrovirus-2 (SRV-2). Three of the four blood recipients died with SAIDS at 13, 15, and 26 weeks postinoculation. The fourth animal is alive with SAIDS. All four test monkeys became viremic and produced antiviral antibody. None of the inoculated monkeys produced measureable neutralizing antibody to SRV-2. The survivor produced higher levels of antiviral antibody than the monkeys that died. Phytohemagglutinin and concanavalin A reactivity of peripheral blood lymphocytes was depressed from weeks 6 to 12 after inoculation. Clinical findings included development of splenomegaly in all four monkeys, and diarrhea in two monkeys. Blood counts remained within the normal range except for a depression in the number of polymorphonuclear lymphocytes in two monkeys. Hematocrits were decreased in two monkeys just prior to their death. All four test monkeys developed lymph node atrophy and bone marrow hypoplasia. Total proteins and immunoglobulin production were normal. This report provides evidence that SRV-2, as well as other type D retroviruses, causes SAIDS in macaque species.

Acquired Immunodeficiency Syndrome↗
PubMed1986

Immunohistochemical study of islet amyloid in diabetes mellitus.

Amyloid was isolated from islets of amyloidotic pancreata of monkey and human beings by solubilization of non-amyloid materials from the pancreas and digestion of contaminating collagen and elastin. The resulting pellet was estimated to be greater than 90% pure islet amyloid. Antibodies specific for monkey islet amyloid and for monkey and human liver amyloid A (AA) were raised in rabbits. Immunohistochemical reaction using the peroxidase antiperoxidase method demonstrated that amyloidotic pancreas reacted with both anti-AA and anti-islet amyloid antibodies. Although the antibodies are specific toward antigens, they cross-react with tissues from human and monkeys. The immunochemical results suggest the possibility that more than one kind of amyloid is associated with islet amyloidosis, but that a significant portion of the islet amyloid is related to AA. Preliminary chemical analysis indicated that islet amyloid is enriched with hexosamines while AA contains both hexosamines and hexoses. Establishment of the islet amyloid composition(s) can give insight into its source and its role in diabetes in Macaca nigra and human beings.

Amyloid↗
PubMed1986

Changes in islet cell composition during development of diabetes in Macaca nigra.

The islets of Langerhans in sections from the pancreas tail of Macaca nigra were stained by antiserum to insulin, glucagon, or somatostatin. The area of stained cells per total area of the islets was determined by a computerized photometric method. Insulin of the beta cells occupied 77% of the islet area in nondiabetic (ND) monkeys and decreased to 62% in monkeys in the earliest stages of metabolic deterioration, i.e., hormonally impaired (HI) monkeys. At the later stage of borderline diabetes (BD), monkeys had only 39% of the islet area occupied by insulin and the area was diminished to less than 1% in diabetic (D) monkeys. Islets in HI monkeys had an unusual pattern in which only the beta cells in the periphery of islets were stained. Glucagon in the alpha cells stained 7% of the islet area in ND monkeys, but the area was almost doubled to 13% in HI monkeys; the percentage decreased to about 5% in BD and 3% in D monkeys. Somatostatin accounted for 5% of the islet area in ND monkeys, was slightly greater at 7% in HI monkeys, and decreased to 3% in BD and 2% in D monkeys. Alterations in percentages of secretory cells correlated with several of the metabolic and clinical changes.

Animals↗
PubMed1986

Association of SAIDS/RF-related signs with current or past SAIDS type 2 retrovirus infection in a colony of Celebes black macaques.

The 83 members of the Celebes black macaque (Macaca nigra) colony were screened for viremia with simian acquired immunodeficiency syndrome (SAIDS) type 2 retrovirus and antibodies against the retrovirus. On the basis of this screening, the Celebes colony was divided into four groups: retrovirus-positive/seropositive (virus+/Ab+); retrovirus-negative/seropositive (virus-/Ab+); retrovirus-positive/seronegative (virus+/Ab-); and retrovirus-negative/seronegative (virus-/Ab-). Monkeys in the virus+/Ab+ group displayed more major clinical signs and required medication more times than monkeys in the other groups. In contrast, monkeys in the virus-/Ab- group had fewer health problems than monkeys in the other groups. The five monkeys that had surgically confirmed retroperitoneal fibromatosis (RF), palpable abdominal masses, or both, were in the virus+/Ab+ group. Some of the monkeys in groups with current or past retrovirus infection were well clinically. There were no statistically significant differences in the mitogen reactivities of mononuclear cells obtained from monkeys of the different groups.

Acquired Immunodeficiency Syndrome↗
PubMed1986

Relationship of mitogen reactivity to type D retrovirus infection in Celebes black macaques (Macaca nigra).

The Celebes black macaque (Macaca nigra) colony at the Oregon Regional Primate Research Center has a high incidence of an immunodeficiency syndrome characterized by recurrent diarrhea and the development of retroperitoneal fibromatosis (RF). We have examined the relationship of type D viral infection to the immunodeficiency syndrome by surveying the colony for viral infection and for mitogen reactivity. Type D virus-positive monkeys (28% of the colony) have a higher prevalence of diarrhea, splenomegaly, lymphadenopathy and weight loss than do virus-negative monkeys, and RF has been found to occur only in virus-positive animals. Comparison of the concanavalin A (con-A) and phytohemagglutinin reactivities of the virus-positive and -negative populations has revealed no significant difference. However, within the virus-positive population, those with RF have reduced con-A reactivity and there are both high and low mitogen responders in the groups lacking RF. Thirty-two percent of the virus-positive monkeys are free of clinical symptoms, 40% have clinical symptoms but no RF, and 27% have clinical symptoms and RF. Five of the six monkeys with RF are older than the RF-free monkeys but monkeys are susceptible to type D retrovirus infection regardless of age or sex. The progressive nature of this immunodeficiency syndrome, its broad age range, and the probability that the etiological agent is also a type D retrovirus and the similarity of RF to Kaposi's sarcoma make this a potentially useful model for human AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed1986

Effects of intravenous epinephrine on macaque platelets.

Blood was obtained from three species of macaques for a study of platelets. A rapidly mobilizable platelet pool was demonstrated in rhesus macaques given intravenous epinephrine. The number of platelets/ml of blood increased about 30% 3 to 5 min after epinephrine was given. The size distributions of the platelets were similar before and after injection. Platelet aggregability was increased after injection. Basal platelet aggregabilities, as measured by platelet aggregate ratios, were similar in rhesus macaques. Celebes black macaques, and human subjects, but were significantly greater in cynomolgus macaques than in the other three species.

Adult↗
PubMed1986

Neutralizing antibody prevents type D retrovirus viremia in Celebes black macaques.

The Celebes black macaque (Macaca nigra) colony at the Oregon Regional Primate Research Center has a high incidence of simian acquired immunodeficiency syndrome (SAIDS-RF) that may be caused by type D retrovirus type 2 (SRV-2). During the spring and autumn screening of the colony, seven monkeys previously aviremic were found to be viremic on the basis of the Raji co-culture assay. These monkeys and control groups were selected for further study, which included titration of neutralizing antibody activity and immunofluorescent antibody (IFA) activity before and at the time that the animals became viremic. Results indicated that neutralizing antibody was not present before or at the time that monkeys became viremic and that control monkeys who were IFA+ and did not become viremic had high levels of neutralizing antibody. The IFA titre did not change significantly or predictably at the time the animals became viremic.

Acquired Immunodeficiency Syndrome↗
PubMed1985

Metabolism of arachidonic acid by macaque platelets. Implications for studies on atherosclerosis.

The metabolism of [1-14C]arachidonic acid [( 1-14C]AA) by washed platelets from macaques and human subjects was investigated. The results were as follows: At substrate levels of 1 microM, similar amounts of prostaglandin E2 (PGE2), prostaglandin F2 alpha (PGF2 alpha), prostaglandin D2 (PGD2), and thromboxane A2 (TXA2), measured as thromboxane B2 (TXB2), were produced from [1-14C]AA by platelets from rhesus, Celebes black, and cynomolgus macaques and humans. An increase in the AA concentration from 1 microM to 20 microM decreased the TXB2: PGD2 ratio (aggregator: antiaggregator) from greater than 5 to less than 2 in all series. In the human series, the ratio decrease was due to an increase in PGD2 production; in the macaque series, PGD2 production increased and TXB2 production decreased. Under basal conditions and at 1 microM AA concentrations, the amounts of prostaglandins and thromboxanes produced by platelets from male and female rhesus macaques were the same. An increase in substrate concentration from 1 microM to 20 microM AA decreased TXB2 production and increased PGD2 production to the same extent in platelets from male and female rhesus macaques. Imidazole increased prostaglandin production and decreased TXB2 production by platelets from both male and female rhesus macaques. The TXB2: PGD2 ratios were reduced below 1.5; there was no difference between the ratios in the two series. In the presence of 1 mM imidazole, greater amounts of prostaglandins and thromboxanes were produced in the male than in the female series. These data indicate that macaque's platelets are a suitable model for the study of AA metabolism in human platelets.

Animals↗