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Biomedical subjects

M A Miller

Publications and source records attributed to M A Miller.

At least 199 records · Page 11Linked to original sources

The development of parenting: nursing resources.

Successful parenting has a major impact on the emotional well-being and cognitive development of young children. Infants gain their sense of self at an early age through their interactions with their caregivers. Nurses can play a unique role in helping parents and caregivers learn about their infant's abilities and behavior and in providing interventions to foster positive parent-infant interactions. Several resources are presented that the professional can use to help parents learn about their newborn's individual communication patterns and needs.

Child Development↗

Growth inhibition of Mycobacterium tuberculosis by polyoxyethylene stearate present in the BACTEC pyrazinamide susceptibility test.

We have previously found that approximately 3.5% of 428 clinical isolates of Mycobacterium tuberculosis yield uninterpretable results in the BACTEC pyrazinamide (PZA) susceptibility test system, because of inadequate growth. We tested the hypothesis that polyoxyethylene stearate (POES), the ingredient of the reconstituting fluid for the test, was the cause of this growth inhibition. A total of 15 isolates known for their previously uninterpretable results and 100 randomly chosen clinical isolates were tested in parallel both with and without POES. Repeat testing of the isolates with previously uninterpretable results yielded results in the presence of POES in only seven (47%). In the absence of POES, all gave interpretable results but one such result showed false resistance. For the other 100 clinical isolates, interpretable results were obtained with and without POES, but growth was enhanced in the absence of POES, especially in the PZA-susceptible strains. This was evidenced by a decreased time to attain a growth index of 200 in the control vial (4.9 days without POES versus 5.8 days with POES; P < 0.001) and a higher mean growth index ratio on the day of interpretation of the test (7.4% without POES versus 2.2% with POES; P < 0.001). However, the enhanced growth without POES led to 20 susceptible strains being misinterpreted as either resistant or borderline. We suggest that isolates of M. tuberculosis which yield uninterpretable results in the BACTEC PZA test system should be retested both with and without POES. If interpretable results indicating PZA resistance are obtained only in the absence of POES, the result should be confirmed by a pyrazinamidase assay or by the conventional proportion method. Routine omission of POES from the BACTEC test for all clinical strains is discouraged because of the unacceptably high false-resistance rates.

Antitubercular Agents↗

Autoradiographic localization of nitric oxide synthase binding sites in normal and diabetic rat corpus cavernosum.

OBJECTIVES: To investigate density and distribution of nitric oxide synthase (NOS) binding sites in rat cavernosal tissue, and to assess any changes brought about by the onset of diabetes mellitus. METHODS: Hyperglycaemic non-ketonuric diabetes mellitus was induced in 5 rats using streptozotocin. The penises were excised from these rats 2 months after the administration of streptozotocin and stored at -70 degrees C. Longitudinal serial sections (6 microns) were cut in a cryostat and thaw mounted onto gelantinized microscope slides. Low- and high-resolution autoradiography was performed using a radioligand for NOS. Densitometric analysis was performed on the autoradiographs and the results compared with those obtained from 5 age-matched no-diabetic rats. RESULTS: NOS binding was primarily localized to the endothelium lining the cavernosal lacunar spaces. Significantly increased binding of NOS was seen in the diabetic cavernosal tissue 2 months after induction of diabetes mellitus. CONCLUSIONS: NOS binding is present on the endothelium of the rat corpus cavernosum and is increased in diabetic rats 2 months after streptozotocin administration. This increase in NOS binding may be part of the endothelial dysfunction which is reported in the corpus cavernosum of diabetic patients or rats.

Animals↗

Histologic and immunohistochemical characterization of hemangiomas in the skin of seven young horses.

The histologic and immunochemical characteristics of benign vascular tumors excised from the skin of seven young horses were evaluated. The patients were male horses of various breeds and were 16 months of age or younger at the time of presentation. Six tumors occurred on the extremities, and one was removed from the lip. Histologically, most tumors consisted of cellular nodules of varying compactness with few to many blood-filled lumina. Nodular growth separated preexisting adnexa and subcutaneous collagen. Some tumors contained or consisted predominantly of loosely packed arrays of ramifying, veins, and capillaries separated by collagen within the dermis and subcutis. Within areas of nodular growth, multilayered vascular walls were encircled by reticulin strands that surrounded the endothelium and adjacent pericytes and also separated nonperivascular cells in the mass. Immunohistochemical staining of factor-VIII-related antigen and labeling by Ulex europeus-1 lectin was restricted to an innermost layer of cells surrounding vascular spaces, confirming their vascular endothelial origin. The plump fusiform cells arranged concentrically around the endothelium and some of those unassociated with vascular lumina stained with antibody to alpha-smooth muscle actin, as did the muscularis of larger vessels inside and outside of tumor nodules. These findings demonstrate an orderly arrangement between endothelium and supportive cells in these benign vascular neoplasms of young horses, similar to that observed during vascular development.

Actins↗

Discrimination of methadone and cocaine by pigeons without explicit discrimination training.

Pigeons were trained to peck a key on a variable-interval 2-min schedule of food reinforcement. Prior to each session, either 2.0 mg/kg methadone (n = 3), 3.0 mg/kg cocaine (n = 4), or 5.6 mg/kg cocaine (n = 2) was administered. When each pigeon's rate of pecking was stable, a range of doses of the training drug and saline were administered prior to 20-min extinction sessions separated by at least four training sessions. Rate of pecking during these extinction tests was generally an increasing function of dose, with the lowest rates obtained following saline and low doses and the highest rates obtained following doses near the training doses. Dose functions from pigeons trained with 5.6 mg/kg cocaine were steeper than those from pigeons trained with 3.0 mg/kg cocaine. Pigeons trained with methadone or 3.0 mg/kg cocaine were then given discrimination training, in which food reinforcement followed drug administration and 20-min extinction sessions followed saline administration. Rates of pecking under these conditions quickly diverged until near-zero rates were obtained following saline and high rates were obtained following drug. Discrimination training steepened dose functions for the training drugs, and the effects of several other substituted drugs depended on the pharmacology of the training drug. The pigeons trained with 5.6 mg/kg cocaine were tested with d-amphetamine, methadone, and morphine prior to discrimination training. d-Amphetamine increased rates dose dependently, and methadone and morphine did not. The results suggest that discriminative control by methadone and cocaine was established without explicit discrimination training.

Animals↗

Peripheral portal venous blood flow alterations induced by hepatic masses: evaluation with color and pulsed Doppler sonography.

We examined 29 patients with intra- and extrahepatic masses and 10 normal volunteers with duplex and color Doppler ultrasonography. Portal blood flow adjacent to the masses was categorized as anterograde, retrograde, or nondetectable and was correlated with lesion size, character, and location. Anterograde flow was documented in the main portal vein and in the central right and left portal veins in all patients and volunteers. Flow in the peripheral portal veins near the lesion examined was retrograde in 17, anterograde in 10, and nondetectable in two of the patients. Retrograde peripheral flow was seen only in solid lesions, abscesses, and large subcapsular hematomas. Peripheral portal flow was anterograde in all of the volunteers. This study confirms that color Doppler sonography can detect alterations in portal flow induced by intra- and extrahepatic masses. The relatively common presence of peripheral portal flow reversal in patients with metastases and hepatocellular carcinomas indicates that it is not a reliable sign for differentiation between these entities.

Adult↗

Influence of age, gender, and menstrual cycle on the normal electrogastrogram.

OBJECTIVES: Dyspeptic symptoms, which are more prevalent in females, are associated with gastric myoelectric and motor abnormalities. Age, gender, and menstrual cycle affect gastric emptying, but their effects on gastric myoelectric activity are not well characterized. The aim of this study was to determine the effects of age, gender, and menstrual cycle on gastric myoelectric activity. METHODS: Healthy subjects (34 male, 49 female; ages 20-79 yr) underwent cutaneous electrogastrography with 60-min fasting and 60-min postprandial recordings. Premenopausal females were studied during days 1-3, 8-10, and 18-20 after onset of menses. Dominant slow wave frequency (DF), power of the DF, and percent time the DF was in a 2- to 4-cpm rhythm were determined for fasting and postprandial periods. RESULTS: The DF, power of the DF, and percent time the DF was in a 2- to 4-cpm rhythm increased from the fasting to the postprandial period. The postprandial increase in the DF was less in females (5.3 +/- 1.2%) than in males (13.0 +/- 2.6%; p < 0.01). In premenopausal females, the DF increased from fasting to the postprandial period for days 1-3 (6.6 +/- 1.5%; p < 0.01) and 8-10 (6.6 +/- 2.3%; p < 0.01), but not during days 18-20 of the menstrual cycle (1.3 +/- 1.8%). The postprandial frequency increase in DF was less for male subjects > or = 60 yr (3.8 +/- 4.0%) than for males < 60 yr (14.6 +/- 2.8%; p < 0.05). CONCLUSIONS: The DF of the electrogastrogram is affected by age, gender, and phase of the menstrual cycle. The influence of these factors should be recognized when interpreting electrogastrograms in symptomatic patients.

Adult↗

Surfactant proteins and thyroid transcription factor-1 in pulmonary and breast carcinomas.

Antibodies to the pulmonary epithelial cell-specific proteins surfactant proteins A and B (SP-A and SP-B) and to thyroid transcription factor-1 (TTF-1), a homeodomain nuclear transcription protein, were used as immunohistochemical markers to asses their ability to distinguish primary pulmonary non-small cell carcinomas (n = 57) from carcinomas of the breast (n = 51). SP-A, SP-B, and TTF-1 were detected in 49%, 53%, and 63% of non-small cell carcinomas, respectively. These three antibodies stained pulmonary adenocarcinomas in 54%, 63% and 76% of specimens, respectively. Squamous cell carcinomas rarely stained using these markers. Antibodies to SP-B and TTF-1 never stained any of the 51 breast carcinomas, whereas four of these tumors stained for SP-A. To better define the potential diagnostic value of these antibodies, 13 breast carcinomas metastatic to the lung were studied. Of the three antibodies tested, only TTF-1 seemed useful, because none of the 13 metastatic tumors showed immunoreactivity to this antibody, whereas six specimens (46%) showed reactivity for both SP-A and SP-B. To emphasize further the potential usefulness of antibodies to TTF-1, sections of adenocarcinomas of the colon (n = 18) and prostate (n = 9), renal cell carcinomas (n = 8), and epithelioid mesotheliomas (n = 4) were evaluated; none was positive. Only one of 66 gastric and one of eight endometrial adenocarcinomas showed focal positivity. These results demonstrate the usefulness of immunodetection of a pulmonary cell selective transcription protein (TTF-1) in the diagnosis of pulmonary adenocarcinoma, readily distinguishing breast carcinomas from primary pulmonary adenocarcinomas. In contrast, staining for SP-A and SP-B is of limited value, because there is an unacceptably high rate of cross-reactivity between breast carcinomas metastatic to the lung and primary pulmonary carcinomas. The latter finding illustrates and supports the fact that tumor marker phenotypes might differ in primary and secondary tissue sites.

Adenocarcinoma↗

Glucose load and renal sodium handling in mild essential hypertension on different sodium intakes.

The aims of the present study were to investigate the effects of changes in sodium intake in patients with untreated mild essential hypertension on the hormonal (plasma renin activity and aldosterone) and renal tubular responses to short-term hyperinsulinemia as achieved by an oral glucose tolerance test (OGTT). Fourteen patients with essential hypertension (mean age, 46 years; average blood pressure (BP), 151/96 mm Hg) were studied. After a 1 week run-in period on their usual diet they entered a randomized double-blind crossover study of a week of low (10 mmol/day) vs a week of high (350 mmol/day) sodium intake. On the last day of each diet they underwent a standard 2-h OGTT. Blood and urines were taken hourly and segmental tubular sodium handling was assessed by the endogenous lithium clearance. The results demonstrate that the plasma insulin and glucose response to a short-term oral glucose load were not influenced significantly by the changes in dietary sodium intake. However, the glucose load was associated with marked renal sodium retention in the absence of any change in systemic BP. The reduction in renal sodium excretion was independent of circulating aldosterone but appeared to be due to an increase in renal distal tubular re-absorption.

Adolescent↗

Vascularity of proliferative breast disease and carcinoma in situ correlates with histological features.

The level of vascularity within an invasive breast carcinoma is a predictor of metastatic potential and survival. However, little is known about the vascular potential and prognostic value of angiogenesis in preinvasive breast pathology. Women with proliferative breast disease or carcinoma in situ are at increased risk of developing invasive breast cancer. This relative risk increases in correlation with defined histopathological features. We asked whether these early proliferative lesions and carcinoma in situ were capable of inducing a vascular supply. Vascularity in preinvasive archival paraffin-embedded breast tissue from 90 patients was quantified by immunohistochemical identification of vessels using anti-von Willebrand factor. Vascular scores were analyzed with respect to histopathological diagnosis, age at diagnosis, and presence of coincident invasive disease. These data indicate that: (a) the vascularity of histopathologically normal epithelium is greater in breasts containing invasive disease than in breasts lacking invasive disease; (b) simple proliferative breast disease induces a vascular supply greater than that of normal breast epithelium; and (c) vascularity increases in proportion to epithelial lesion progression and relative risk of invasion. These studies indicate that the vascularity of preinvasive breast pathology may be a clinically useful predictor of invasive breast cancer.

Adult↗

Nonviable bacterial antigens administered with IL-12 generate antigen-specific T cell responses and protective immunity against Listeria monocytogenes.

The development of effective vaccine strategies for intracellular pathogens, including bacteria, viruses, and parasites, is one of the major frontiers of scientific research. For the studies described here, the murine model of Listeria infection was used to evaluate the adjuvant effects of IL-12 when used as an immunization component. These studies revealed that typically nonimmunogenic doses of heat-killed Listeria monocytogenes, or soluble listerial Ag preparations, elicit intense Th1-type Listeria-specific T cell responses when administered i.p. along with recombinant murine IL-12. In addition to the Ag-specific production of IL-2 by CD4+ peritoneal cells that was elicited, several other correlates of protective responses were noted, including dramatic induction of CD3+ and alpha beta TCR+ cell populations in the peritoneal cavity and increased expression of class II MHC and production of IL-12 (upon in vitro restimulation) by peritoneal macrophages. Protection studies demonstrated that the T cell responses elicited by a IL-12-potentiated, heat-killed L. monocytogenes vaccine were sufficient to effectively protect mice against challenge with a large dose of virulent Listeria.

Animals↗

Vasopressin and galanin mRNAs coexist in the nucleus of the horizontal diagonal band: a novel site of vasopressin gene expression.

Vasopressin (VP) neurons have been identified in several brain regions where VP has been hypothesized to act as a neurotransmitter or neuromodulator. In many sites, VP is colocalized with the neuropeptide galanin (GAL). Here, using single in situ hybridization histochemistry, we have identified a novel group of neurons within the nucleus of the horizontal diagonal band of Broca (HDB) that express the VP gene and have assessed the distribution of these cells in adult male and female rats (90 days old, n = 7/group). VP mRNA-expressing neurons were scattered throughout the rostrocaudal extent of the HDB, and the number of VP neurons detected unilaterally ranged from 1 to 17 cells per 20 microns section. Using double in situ hybridization histochemistry on alternate sections, we have assessed the number of cells expressing VP and/or GAL mRNA in the diagonal band and have determined the extent of their colocalization. Approximately 50% of all VP-expressing neurons in the HDB coexpressed GAL mRNA, and 33% of GAL-expressing neurons in this region coexpressed VP mRNA. No sex differences were detected in the number of neurons expressing either VP or GAL mRNA or in the incidence of coexpression of VP and GAL mRNAs in this region. VP neurons in the HDB exhibited a low level of expression, and cellular VP mRNA content did not differ between male and female rats. However, sex differences were present in the bed nucleus of the stria terminalis (BNST) of these same rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Distribution of small vasopressinergic neurons in golden hamsters.

In rats, small (diameter: ca. 10 micrograms) vasopressinergic neurons have been localized in the forebrain, including extrahypothalamic sites, such as the bed nucleus of the stria terminalis (BST) and the medial amygdala (MeA). In golden hamsters, no such neurons have ever been described in extrahypothalamic sites, while their presence in some hypothalamic sites, such as the paraventricular nucleus (PVN), remains controversial. The present studies were carried out to confirm the existence of small vasopressinergic neurons in the forebrain of golden hamsters, using rats as a positive control. The presence of small vasopressinergic neurons in these sites was first tested by immunocytochemistry in colchicine-treated animals. The resulting distribution was corroborated by in situ hybridization for vasopressin (AVP) mRNA. While a large number of small AVP-immunoreactive (AVP-ir) neurons was found in the BST and MeA of colchicine-treated rats, none was found in the same locations in hamsters. Interestingly, as a few large (diameter: 20-25 micrograms) AVP-ir neurons were found in the BST just medial to the small neurons in rats, the same area contained a few large and small AVP-ir neurons in hamsters. In the PVN, large and small AVP-ir neurons were found in rats and hamsters. However, three to four times more neurons were counted in rats. These data were confirmed by in situ hybridization. Indeed, in hamsters, no labelling for AVP mRNA was detected in small neurons within the BST and MeA. Furthermore, the PVN of rats contained more labelling for AVP mRNA, as compared to hamsters. These results confirm that the distribution of vasopressinergic neurons in rats cannot be generalized to other species without a detailed analysis.

Amygdala↗

Regulation of interprotein electron transfer by Trp 191 of cytochrome c peroxidase.

Cytochrome c peroxidase (CcP) reacts with peroxide to form compound I, an intermediate that has an oxy-ferryl iron center and a stable indolyl radical at Trp 191. During the normal catalytic cycle, the oxy-ferryl heme and the Trp 191 radical are reduced by sequential electron transfers from ferrous cytochrome c (Cc). To investigate the role of protein structure in these electron transfer reactions, mutagenesis was used to replace Trp 191 with Phe. The Trp 191-->Phe enzyme [CcP(MI,F191)] reacts with peroxide to form an oxy-ferryl iron center and a transient porphyrin radical. The reaction of Cc from horse and yeast with peroxide-oxidized CcP(MI,F191) was characterized under transient and steady-state conditions. The rate of ET from Cc to the oxy-ferryl heme of CcP(MI,F191) was decreased by at least 10,000-fold relative to the CcP(MI) parent. This effect was observed at 20 and 100 mM ionic strength, with both yeast and horse cytochrome c as the substrate. Thus, Trp 191 is a critical component of all pathways that permit rapid reduction of the oxy-ferryl heme by Cc under these conditions. The reaction of the porphyrin radical with Cc was difficult to characterize, owing to the short half-life of this intermediate. The oxidation of Cc by this intermediate had a maximum rate constant of 32 s-1 at pH 6.0, 25 degrees C. Circumstantial evidence suggests that the porphyrin radical is not directly reduced by Cc, but is instead reduced via a protein-based radical intermediate. The steady-state activity of the mutant enzyme was 300-600-fold lower than the CcP(MI) parent, but kcat is 7-20 times greater than the rate constant for reduction of the oxy-ferryl heme under all conditions examined. Thus, the oxy-ferryl heme is not reduced to the ferric state under steady-state conditions. Transient changes in the absorption spectrum further indicate that steady-state oxidation of Cc2+ by CcP(MI,F191) occurs via reaction of peroxide with the oxy-ferryl enzyme.

Animals↗

Chyloabdomen in a neonatal foal.

A 12-hour-old female standardbred foal developed signs of abdominal pain, tachycardia, tachypnoea and fever associated with chylous ascites. Small intestinal obstruction was due to segmental, mid-jejunal lymphangiectasia. Post mortem examination revealed a lack of communication between afferent and efferent lymphatic vessels in the mesenteric lymphocentre, a defect which was suspected to be congenital.

Abdominal Pain↗