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Biomedical subjects

A M Carpenter

Publications and source records attributed to A M Carpenter.

At least 19 recordsLinked to original sources
PubMed2000

Specificity of a new lipid mediator produced by testicular and peritoneal macrophages on steroidogenesis.

Macrophage-derived factor (MDF) is a lipophilic factor produced by rat testicular and peritoneal macrophages that maximally stimulates testosterone production by rat Leydig cells through a steroidogenic acute regulatory protein independent mechanism. The purpose of the present study was to determine whether MDF is also produced by human macrophages, and/or if it acts on human steroidogenic cells. We also studied the tissue-specific functions of MDF by determining if it also acts on steroidogenic cells of the ovary and adrenal glands and, if so, does it require new protein synthesis. It was found that MDF was produced by human peritoneal macrophages, and was capable of stimulating human steroidogenic cells. In terms of tissue specificity, it was found that primary cultures of rat adrenocortical cells respond to MDF with increased secretion of aldosterone and corticosterone, as did rat granulosa cells by producing progesterone. MDF acted in the presence of cycloheximide, indicating that it does not require new protein synthesis. These results indicate that MDF may have significant therapeutic potential and provide a basis for future studies concerning its physiological role in humans. These results further suggest that MDF is not only involved in paracrine regulation of Leydig cells, but also has the potential for the local regulation of steroidogenesis in both granulosa and adrenal cortical cells.

Adrenal Glands↗
PubMed1998

Alterations in brain and pituitary beta-endorphin content in genetically epilepsy-prone rats.

We measured beta-endorphin concentrations in the anterior and neurointermediate lobes of the pituitary gland and in microdissected brain regions of moderate-seizure genetically epilepsy-prone rats (GEPR-3), severe-seizure GEPR-9s and Sprague-Dawley non-epileptic control rats. Plasma concentrations of beta-endorphin and beta-melanocyte-stimulating hormone (alpha-MSH) were also measured as indicators of pituitary POMC-peptide secretion. Concentrations of beta-endorphin in the anterior lobe of GEPR-3s were 53% higher compared to controls and 57% higher compared to GEPR-9s. There were no differences in neurointermediate lobe beta-endorphin concentrations between control and either GEPR strain. Plasma beta-endorphin concentrations were significantly lower in GEPR-9s than controls. Plasma levels of alpha-MSH did not differ between control and GEPRs. In the hypothalamus of GEPR-9s beta-endorphin concentrations in the arcuate nucleus were significantly greater than in GEPR-3s. Concentrations of beta-endorphin in the central amygdala of GEPR-9s were two- to threefold greater than in control or GEPR-3s. Beta-Endorphin concentrations in the central gray of GEPR-3s were 58% lower than control or GEPR-9s. These data suggest that anterior lobe beta-endorphin secretion is reduced in GEPR-9s. Furthermore, brain endorphinergic pathways appear to be differentially altered in GEPR-3s and GEPR-9s. Alterations in pituitary beta-endorphin secretion and brain endorphinergic systems may contribute to seizure susceptibility in GEPRs and to differences in seizure severity between GEPR-3s and GEPR-9s.

Animals↗
PubMed1998

Regulation of Leydig cells through a steroidogenic acute regulatory protein-independent pathway by a lipophilic factor from macrophages.

The purpose of this investigation was to study the mechanism of action of a macrophage-derived factor that stimulates steroid production by Leydig cells. This factor increased testosterone production within 30 min, and reached a half-maximal response by 6-8 h. At a maximal dose, it stimulated testosterone production 20-fold at 24 h. Its efficacy was consistently higher than that achieved with a maximal dose of human chorionic gonadotropin (hCG). However, Leydig cells treated with a maximal dose of both the macrophage-derived factor and hCG secreted the same amount of testosterone as when given a maximal dose of only the macrophage-derived factor. The macrophage-derived factor did not require new protein synthesis to stimulate testosterone production, nor did it alter the amount of steroidogenic acute regulatory protein (StAR). While the macrophage-derived factor required an active cholesterol side-chain cleavage complex system, it did not alter the capacity of this enzyme complex. Finally, the macrophage-derived factor was unable to stimulate the production of progesterone by isolated mitochondria. In summary, the macrophage-derived factor is a highly active, acute regulator of steroidogenesis that acts through a high capacity StAR-independent pathway.

Aminoglutethimide↗
PubMed1996

The effects of melanocortin peptides and corticosterone on habituation in the great plains toad, Bufo cognatus.

We investigated the ability of various melanocortin peptides and corticosterone to influence habituation of prey-catching behavior in the toad, Bufo cognatus. Male toads were injected with various melanocortin peptide fragments or corticosterone 30 min prior to acquisition. Adrenocorticotropin (ACTH[1-39]), ACTH[4-10], and N-acetyl ACTH[1-13] amide (alpha-MSH) significantly decreased the number of turning reactions during acquisition in relation to controls. The effects of the noncorticotropic ACTH fragments were rapid and transient, occurring within the first 20 min of acquisition. Corticosterone caused a slight but significant decrease in the number of turning reactions. Neither des-acetyl alpha-MSH nor (Nle4, D-Phe7) alpha-MSH had any effect on acquisition. ACTH[1-39] was the only peptide that delayed extinction. The ability of alpha-MSH to facilitate acquisition was not observed in the presence of the alpha-MSH antagonist U-76188E. These data suggest that the effects of ACTH on habituation are, in part, independent of effects on glucocorticoid secretion. Apparently, similar structural requirements are necessary for the behavioral effects of melanocortins in amphibians and mammals.

Adrenocorticotropic Hormone↗
PubMed1995

Diurnal variation in alpha-melanocyte-stimulating hormone content of various brain regions and plasma of the Texas toad, Bufo speciosus.

We measured the concentrations of alpha-melanocyte-stimulating hormone (alpha-MSH) in various brain regions as well as in the pituitary gland and plasma of the toad Bufo speciosus during a 24-hr light:dark cycle. There was significant diurnal variation of alpha-MSH concentrations in the hypothalamus and brainstem. In both areas alpha-MSH concentrations were highest during the scotophase. Peak alpha-MSH concentrations in the hypothalamus were observed at 21.00 and 05.00 hr, while a single peak in alpha-MSH concentrations was observed in the brainstem at 21.00 hr. In contrast, peak alpha-MSH concentrations in the plasma were observed during the photophase at 17.00 hr, when brain concentrations of alpha-MSH were low. There was no significant diurnal variation observed in the pituitary content of alpha-MSH throughout the 24-hr light:dark cycle. These data suggest that different mechanisms control hypothalamic and pituitary alpha-MSH cells in the toad during the 24-hr light:dark cycle. The fact that peak alpha-MSH concentrations were observed in the hypothalamus during the activity period of the toad is consistent with the proposed role of alpha-MSH peptides in learning and memory processes.

Animals↗
PubMed1993

Glomerulosclerosis in type 2 (non-insulin-dependent) diabetes mellitus: relationship to glycaemia in the University Group Diabetes Program (UGDP).

Kidney tissue of acceptable quality was available from autopsies of 55 patients who had been followed prospectively for 3 to 15 years as participants in the University Group Diabetes Program, a study of vascular disease in Type 2 (non-insulin-dependent) diabetic patients. Slides were prepared for light microscopic reading by uniform histologic techniques, and then were randomly intermixed and coded with tissues identically prepared from matched non-diabetic subjects (morphologic controls). After independent review by three morphologists, the results were tabulated and assigned to one of four diagnostic groups: 1) typical diabetic nodular glomerulosclerosis; 2) mesangial changes suggestive of diabetes (diffuse lesion); 3) non-diabetic renal disease; 4) normal for age. Of the diabetic cases 31% (17 of 55) were found to show nodular glomerulosclerosis, and another 47% (26 of 55) showed suggestive changes; none of the morphologic control slides was read as showing nodular glomerulosclerosis, but some were judged to show suggestive mesangial (diffuse) changes. Although only 4 of the 17 diabetic patients with nodules had died of uraemia, many had hypertension, which may have contributed to their deaths from vascular disease. The patients with nodular glomerular changes also showed, on the average, the highest blood glucose levels during life. Type 2 diabetes in later life appears to be associated with a high risk for typical tissue changes of diabetic kidney damage, which may contribute significantly to morbidity and mortality and may be present before azotaemia and qualitative proteinuria have been recognized.

Autopsy↗
PubMed1989

Ultrastructural studies of the human round window membrane.

An ultrastructural study of 14 round window membranes of seven human ears disclosed three basic layers: an outer epithelium lining the middle ear, a middle core of connective tissue, and an inner epithelium bordering the inner ear. Morphological evidence suggests that these layers participate in absorption and secretion of substances to and from the inner ear. A comparison of morphological features of round window membranes suggests that the average thickness of 70 microns does not change with advancing age. However, in the elderly, the connective tissue has a looser arrangement; there is an increase in ground substance; and elastic fibers thicken. Fibroblast nuclei become larger, rounder, and less uniform and have extensions. The ultrastructure of the "false round window membranes," with epithelial cells of the same type bounding both sides, suggests that these membranes consist of juxtaposed epithelial folds of the overlying promontory.

Aging↗
PubMed1987

Ultrastructural studies of the round-window membrane of the cat.

An ultrastructural study of eight round-window membranes of four normal cats disclosed three basic layers: an outer epithelium (middle ear), a middle core of connective tissue, and an inner epithelium (inner ear). Morphologic evidence suggests that these layers participate in absorption and secretion of substances to and from the inner ear, such that the entire membrane could play a role in an inner ear "defense system." A comparison of morphologic features of round-window membranes from cats, rodents, and human beings suggests that the cat is a superior animal model for experimental studies. Cationic ferritin, placed for two hours in the round-window niche of four normal cats, was observed to traverse the round-window membrane through pinocytotic vesicles into the connective tissue layer. Evidence of exocytosis of tracer by the inner epithelial layer into the scala tympani is presented. When placed in perilymph, this same tracer was incorporated by inner epithelial cells, suggesting absorptive capabilities of the round-window membrane.

Animals↗
PubMed1983

Light microscopic morphometric analysis of rat ileal mucosa. I. Component quantitation of IgA-containing immunocytes.

A light microscopic morphometric analysis of IgA-containing immunocytes within samples of ileal mucosa was performed. The following groups of rats were studied: (1) animals raised in a gnotobiotic environment (microbial reduction); (2) animals with iatrogenic self-filling intestinal blind loops (microbial proliferation); and (3) control animals (sham operation). The unlabeled antibody enzyme immunohistochemical localization technique was employed for the identification of intracellular IgA. Component quantitation involved use of a micrometer component quantitator. Numerical density of the immunocyte population was determined by component quantitation of individual and total immunocyte volumes and by application of the Floderus equation. The methodology employed provided a precise quantitative analysis of all mucosal components of normal and manipulated rat ileum. A statistically significant reduction in the volume percentage of IgA-containing immunocytes in association with both microbial reduction and microbial proliferation was observed. The volume percentage reduction of the IgA-containing immunocyte population associated with gnotobiosis may reflect decreased microbial antigenic stimulation, whereas that associated with microbial proliferation may reflect the presence of an increased population of immunocytes producing non-IgA immunoglobulins.

Animals↗
PubMed1982

Ganglia and ganglion cells in the middle ear. Their presence in the human and the cat.

One hundred human and 100 cat temporal bones were studied for the presence of ganglia and/or ganglion cells. These structures were found at the following two main locations: (1) the promontory wall, both anterior to and below the stapes, and (2) the vertical portion of the facial nerve. In the cat, additional ganglion cells were found within the capsule of the musculus tensor tympani, proximal, medial, and lateral to muscle fibers. The consistent presence of ganglion cells in the mucoperiosteum suggests that they play important roles in the middle ear itself; their presence in the vertical portion of the facial nerve supports the concept that the parasympathetic innervation of the parotid gland is not exclusively via the ninth nerve and/or lends anatomical support to atypical facial pains.

Animals↗
PubMed1982

Light microscopic morphometric analysis of rat ileal mucosa: II. Component quantitation of Paneth cells.

A quantitative light microscopic morphometric analysis of lysozyme- and IgA-containing Paneth cells within the ileal mucosa of physiologically manipulated and control (sham operation) animals was performed. The experimental groups of rats included animals raised in a gnotobiotic environment (microbial reduction) and animals with ileal self-filling blind (microbial proliferation) and Thiry-Vella (intestinal discontinuity) loops. The unlabeled antibody enzyme immunohistochemical localization technique was employed for the identification of intracellular lysozyme and IgA. Component quantitation was performed by use of a micrometer component quantitator. Marked Paneth cell hyperplasia was noted in association with gnotobiosis and with the Thiry-Vella fistula. This observation quantitatively confirms previous subjective impressions of increased Paneth cell differentiation in association with those physiologic states. Since the neurovascular component of the Thiry-Vella fistula is intact, the normal intraluminal succus entericus would appear to be involved in modulation of Paneth cell differentiation. The recognition of Paneth cell hyperplasia in association with the Thiry-Vella fistula suggests that this may be a useful experimental model for an evaluation of the life cycle and functional characteristics of this cell population. The results also revealed that no significant change in the volume percentage of Paneth cells and a decreased volume percentage of Paneth cells containing IgA occurred in association with the self-filling blind loop. A decreased volume percentage of IgA-containing immunocytes in association with the blind loop has previously been reported. The data are most consistent with the interpretation that the Paneth cell and immunocyte response to antigenic stimulation are interrelated and that the Paneth cell population has a restricted latitude of response to microbial proliferation.

Animals↗
PubMed1981

Passage of albumin from the middle ear to the inner ear in otitis media in the chinchilla.

A study of the permeability of the middle ear-inner ear interface for macromolecules was carried out in chinchillas with open and obstructed eustachian tubes utilizing tritiated human serum albumin and immunoelectrophoresis. Tritiated albumin was placed in the round window niche area or normal animals and animals in which the eustachian tubes had been obstructed for 24 hours or 14 days. The tritiated albumin was allowed to remain in the middle ear cavity for 24 hours, Samples of middle ear effusion, perilymph, blood and cerebrospinal fluid were collected and measured for radioactivity. Radioactivity was demonstrated in the perilymph. Samples of middle ear effusions and perilymph were also studied by immunoelectrophoresis with goat antihuman albumin. Albumin placed in the round window niche of an experimental animal could be recovered unchanged in the perilymph. The results suggest a pathophysiologic explanation for the association of otitis media and sensorineural hearing loss or endolymphatic hydrops.

Animals↗
PubMed1980

Ganglia and ganglion cells in the middle ear of the cat: preliminary report.

Twenty-five temporal bones of cats were studied for the presence of ganglia and/or ganglion cells in the middle ear. These structures were found at the following three main locations: (1) the promontory wall, both anterior to and below the stapes; (2) the capsule of the musculus tensor tympani, proximal, medial, and lateral to muscle fibers; and (3) the vertical portion of the facial nerve. To the best of our knowledge, ganglion cells in the capsule of the musculus tensor tympani, which is located proximal and lateral to the muscle fibers, have not been described previously.

Animals↗
PubMed1980

Permeability of the round window membrane in otitis media.

A round window membrane permeability study of macromolecules in otitis media, using tritiated normal human serum albumin, was done in cats. Eustachian tube obstruction was used to induce otitis media in ten animals. Samples of perilymph in obstructed and normal control ears were studied after 25 minutes of exposure of the round window to tritiated albumin. Twelve additional animals were obstructed, and their round window membranes studied to provide histopathologic evidence for our permeability studies. In this first report of round windon membrane permeability to macromolecules in otitis media, we observed an increased permeability to tritiated albumin in diseased ears. Evidence suggests a pathophysiological explanation for the association of otitis media and sensorineural hearing loss and/or endolymphatic hydrops. Proof that large molecules pass suggests the feasibility of diffusion of smaller molecules (toxins and enzymes) through the round window membrane.

Animals↗
PubMed1980

Diagnosis of pancreatic islet hyperplasia causing hypoglycemia in a patient with portacaval anastomosis.

A patient with biopsy-proved biliary cirrhosis and previous gastrojejunostomy and portacaval anastomosis experienced episodes of severe hypoglycemia. She was found to have hyperinsulinemia and hyperglucagonemia. An oral glucose tolerance test showed postgastrectomy hypoglycemia. Results of the intravenous tolbutamide test were diagnostic for insulinoma, but results of the intravenous glucagon test and prolonged fast (96 hours) were not. Failure, on two occasions, to suppress C-peptide normally during insulin-induced hypoglycemia led to a diagnosis of pancreatogenous hyperinsulinemia. The pancreas showed a 10-fold increase in islet volume, with intensely positive staining with anti-insulin and anti-glucagon antiserums in addition to anti-somatostatin and anti-pancreatic polypeptide antiserums. Incidental findings at pancreatic exploration were a mesothelioma, which did not stain with anti-insulin antiserum, and, at autopsy one year later, a hepatoma.

Blood Chemical Analysis↗
PubMed1980

Permeability of the middle ear to staphylococcal pyrogenic exotoxin in otitis media.

Middle ear permeability after instillation of staphylococcal pyrogenic exotoxin was studied in each of 12 cats, 6 of them with otitis media induced by obstructing their eustachian tubes. This is the first report that there is passage of toxin to the perilymph, cerebrospinal fluid and blood not only in diseased ears, but also in normal controls, 25 min and 12 h after exposure of the middle ear cavity and round window membrane to toxin. The data suggest a pathophysiological explanation for the association of otitis media and sensorineural hearing loss and/or endolymphatic hydrops; potentially both entities can be caused by exotoxins. It also documents the extraordinary capabilities of movement of staphylococcal exotoxin.

Animals↗
PubMed1980

Otitis media with perforation of the tympanic membrane: a longitudinal experimental study.

Despite the high incidence and prevalence of otitis media, its pathogenesis is not thoroughly understood. In an effort to provide a better understanding of this disease, experimental animal models have been developed which corroborate the changes observed in humans. In this study a new factor was added: tympanic membrane perforation 1 week after Eustachian tube obstruction. Twelve cats were divided in 4 even groups, and sacrificed at 1 and 2 weeks, 1 and 3 months after perforation, and their temporal bones were studied. Findings revealed an early massive reaction of the mucoperiosteum with granulation and polypoidal tissue formation which filled a considerable portion of the middle ear cavity. Polypoidal changes involved the stapediovestibular joint, possibly explaining the cases of stapes fixation found at tympanomastoidectomy procedures for chronic otitis media. Cholesterol granulomas with the classic characteristics as described in humans were observed in all animals at 3 month periods. These were preceded by clefts in the effusions, at 1 month, containing red blood cells. These clefts were considered as probable precursors of cholesterol granuloma formation. The association of endolymphatic hydrops, round window membrane changes, and otitis media without purulent labyrinthitis was observed; however, it was felt that the paucity of animals precluded any definite conclusions.

Animals↗