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Biomedical subjects

S Miller

Publications and source records attributed to S Miller.

At least 397 records · Page 22Linked to original sources
PubMed1990

Dopamine induces light-adaptive retinomotor movements in bullfrog cones via D2 receptors and in retinal pigment epithelium via D1 receptors.

In the eyes of lower vertebrates, retinal photoreceptors and melanin pigment granules of the retinal pigment epithelium (RPE) exhibit characteristic retinomotor movements in response to changes in ambient illumination and to signals from an endogenous circadian clock. We previously reported that 3,4-dihydroxyphenylethylamine (dopamine) mimicked the effect of light on these movements in photo-receptors and RPE cells of green sunfish, Lepomis cyanellus, by interacting with D2 dopaminergic receptors. Here, we report that dopamine also mimics the effect of light on cone and RPE retinomotor movements in bullfrogs, Rana catesbeiana, i.e., dopamine induces cone contraction and RPE pigment dispersion. Dopamine induced cone contraction in isolated dark-adapted bullfrog retinas incubated in constant darkness in the presence of the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (IBMX). This effect of dopamine was inhibited by a D2 but not a D1 antagonist and mimicked by a D2 but not a D1 agonist. These results suggest that induction of cone contraction by dopamine is mediated by D2 dopaminergic receptors and that cone adenylate cyclase activity is inhibited. Thus, dopamine acts via the same type of receptor in both bullfrog and green sunfish retinas to induce cone contraction. In contrast, dopamine influences RPE retinomotor movement via different receptors in fish and bullfrog. Dopamine induced light-adaptive pigment dispersion in isolated dark-adapted bullfrog RPE-eyecups incubated in constant darkness in normal Ringer's solution. Because the retina was not present, these experiments demonstrate a direct effect of dopamine on bullfrog RPE. This effect of dopamine on bullfrog RPE was inhibited by a D1 but not a D2 antagonist and mimicked by a D1 but not a D2 agonist. Furthermore, agents that increase the concentration of intracellular cyclic AMP also induced pigment dispersion in dark-adapted bullfrog RPE-eyecups incubated in the dark. These results suggest that dopamine induces pigment dispersion in bullfrog RPE via D1 dopaminergic receptors. Thus, dopamine acts via different receptors on bullfrog (D1) versus green sunfish (D2) RPE to induce pigment dispersion. In addition, inhibitor studies indicate that pigment dispersion is actin dependent in teleost but not in bullfrog RPE. Dopamine-induced pigment dispersion was inhibited by cytochalasin D in isolated RPE sheets of green sunfish but not in RPE-eyecups of bullfrogs. Together, these observations indicate that dopamine mimics the effect of light on cone and RPE retinomotor movements in both fish and bullfrogs. However, in the RPE, different receptors mediate the effect of dopamine, and different cytoskeletal mechanisms are used to affect pigment transport.(ABSTRACT TRUNCATED AT 400 WORDS)

Adaptation, Physiological↗
PubMed1990

Excitation of the corticospinal tract by electromagnetic and electrical stimulation of the scalp in the macaque monkey.

1. The responses evoked by non-invasive electromagnetic and surface anodal electrical stimulation of the scalp (scalp stimulation) have been studied in the monkey. Conventional recording and stimulating electrodes, placed in the corticospinal pathway in the hand area of the left motor cortex, left medullary pyramid and the right spinal dorsolateral funiculus (DLF), allowed comparison of the actions of non-invasive stimuli and conventional electrical stimulation. 2. Responses to electromagnetic stimulation (with the coil tangential to the skull) were studied in four anaesthetized monkeys. In each case short-latency descending volleys were recorded in the contralateral DLF at threshold. In two animals later responses were also seen at higher stimulus intensities. Both early and late responses were of corticospinal origin since they could be completely collided by appropriately timed stimulation of the pyramidal tract. The latency of the early response in the DLF indicated that it resulted from direct activation of corticospinal neurones: its latency was the same as the latency of the antidromic action potentials evoked in the motor cortex from the recording site in the DLF. 3. Scalp stimulation, which was also investigated in three of the monkeys, evoked short-latency volleys at threshold and at higher stimulus intensities these were followed by later waves. The short-latency volleys could be collided from the pyramid and, at threshold, had latencies compatible with direct activation of corticospinal neurones. The longer latency volleys were also identified as corticospinal in origin. 4. The latency of the early volley evoked by electromagnetic stimulation remained constant with increasing stimulus intensities. In contrast, with scalp stimulation above threshold the latency of the early volleys decreased considerably, indicating remote activation of the corticospinal pathway below the level of the motor cortex. In two monkeys both collision and latency data suggest activation of the corticospinal pathway as far caudal as the medulla. 5. The majority of fast corticospinal fibres could be excited by scalp stimulation with intensities of 20% of maximum stimulator output. Electromagnetic stimulation at maximum stimulator output elicited a volley of between 70 and 90% of the size of the maximal volley evoked from the pyramidal electrodes. 6. Electromagnetic stimulation was also investigated in one awake monkey during the performance of a precision grip task. Short-latency EMG responses were evoked in hand and forearm muscles. The onsets of these responses were approximately 0.8 ms longer than the responses evoked by electrical stimulation of the pyramid.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗
PubMed1990

Neurophysiological observations on corticospinal projections to the upper limb in subjects with Rett syndrome.

The aim of the present study was to investigate the excitability of corticospinal neurons and the integrity of their projections to the alpha motor neurons through the corticospinal tract in subjects of different ages with Rett syndrome. Electromagnetic stimulation of the motor cortex and cervical motor roots was used to evoke motor action potentials in the biceps brachii and hypothenar muscles. The phasic stretch reflex in the biceps brachii was also recorded to study the excitability of spinal alpha motor neurons. Motor cortex stimulation evoked motor action potentials at low threshold and with abnormally short latencies and prolonged durations. In contrast cervical motor root stimulation resulted in responses of normal latency and duration. The phasic stretch reflex had a low threshold, short latency and prolonged duration. It is concluded that in Rett syndrome the corticospinal pathway is intact. The results suggest disordered synaptic control of the Betz cell of the motor cortex and/or the spinal alpha motor neuron, although the involvement of the latter might be a consequence of dysfunction in supraspinal descending motor pathways.

Adolescent↗
PubMed1990

Acute effects of electromagnetic stimulation of the brain on cortical activity, cortical blood flow, blood pressure and heart rate in the cat: an evaluation of safety.

The influence of repeated high intensity electromagnetic stimulation of the brain on cortical activity, cortical blood flow, blood pressure and heart rate has been investigated in the cat, to evaluate the safety of the method. The observations have been made in preparations under propofol anaesthesia before, during and after periods of anoxia. Electromagnetic stimulation of the brain evoked activity in descending motor pathways and was recorded by activity in the median nerve and by muscle twitches. Following repeated series of high intensity stimulation there were no systematic changes in somatosensory evoked potentials or background EEG, nor were there signs of epileptogenic activity during electromagnetic stimulation, before, during or after periods of anoxia. No systematic changes in cortical blood flow, blood pressure or heart rate were observed during electromagnetic stimulation, before or after periods of anoxia. In conclusion, no acute adverse consequences following electromagnetic stimulation in the normal and anoxic cat brain were demonstrated.

Animals↗
PubMed1990

Effect of prostaglandin, leukotriene, and arachidonic acid on experimental otitis media with effusion in chinchillas.

Although previous studies have shown that prostaglandins (PGs), leukotrienes (LTs), and other arachidonic acid (AA) metabolites play an important role in the pathogenesis of otitis media with effusion (OME), the exact role of each AA metabolite in OME is still unknown. The purpose of this study was to examine the effect of several individual AA metabolites alone or in combination and AA itself on experimental otitis media in chinchillas. Normal chinchillas were inoculated daily with normal saline, PGE2, LTC4, LTC4 + PGE2, and AA through the superior bullae over 7 days. Animals were followed by otoscopy and tympanometry, samples of middle ear effusion were collected for biochemical assay, and temporal bones were processed for histopathology. The highest number of ears that developed OME was in the group inoculated with PGE2 + LTC4. The degree of inflammatory change was more pronounced in groups injected with LTC4 than any other group. The findings of this study suggest that eicosanoids PGE2, LTC4, and AA alone or in combination inoculated into the middle ear can induce OME.

6-Ketoprostaglandin F1 alpha↗
PubMed1990

Vocal changes in patients undergoing radiation therapy for glottic carcinoma.

A prospective evaluation of vocal changes in patients receiving radiation therapy for T1 and T2 (AJC) glottic carcinoma was undertaken in January 1987. Vocal analysis was performed prior to radiotherapy and at specific intervals throughout the radiation treatment program. The voicing ratio was extrapolated from a sustained vowel phonation using the Visipitch interfaced with the IBM-PC. Preliminary observations suggested three distinct patterns of vocal behavior: 1. reduced voicing ratio with precipitous improvement within the course of treatment, 2. high initial voicing ratio with reduction secondary to radiation induced edema, with rapid improvement in the voicing component after the edema subsided, and 3. fluctuating voicing ratio during and following treatment. Enrollment of new patients and a 2-year follow-up of current patients was undertaken.

Aged↗
PubMed1990

Selective breeding of dogs for segregation of limb edema from microfilaremia as clinical manifestations of Brugia infections.

Three generations of beagles were monitored for microfilaremia (mf) and clinical disease during repeated infection with Brugia pahangi and were selectively bred for offspring manifesting limb edema and low or amicrofilaremia. A high microfilaremic female mated to a high microfilaremic male produced 7 pups, 6 of which maintained mf greater than 1,000/ml for greater than 2 years after 5 monthly infections of 10 infective larvae each. An uninfected female mated to another high mf male produced 5 pups, 4 of which did not exceed 1,000 mf/ml 7 months after initiation of the repeating infection regimen; 1 of these remained amicrofilaremic after 2 additional challenges. Neither the parents nor the offspring from these matings manifested chronic limb edema. Two matings were conducted with offspring from the microfilaremic female by breeding siblings with the lowest mf and breeding siblings with the highest mf. The high mf siblings produced 4/5 offspring manifesting chronic limb edema (greater than or equal to 7 months duration) and either no mf (in 2 dogs) or less than 100 mf/ml after the repeating infection regimen. The lower mf siblings produced 5 offspring, all with greater than 1,000 mf/ml 6 months after the initiation of the repeating infection regimen; none manifested edema. Comparisons of IgG antibody levels, specific for extracts of adult worms, showed no consistent differences between these 2 litters of dogs that could be associated with limb edema or mf when monitored for 16 months; however, the onset of lymph node enlargement was much earlier in the group of dogs manifesting limb edema than in the other litter.

Animals↗
PubMed1990

Rod electroretinograms in an elevated cyclic guanosine monophosphate-type human retinal degeneration. Comparison with retinitis pigmentosa.

Unusual rod electroretinogram (ERG) intensity-response functions were recorded from three female patients with retinal degeneration who had visual acuities of 20/200, retinal arteriolar narrowing, and diffuse granularity of the retinal pigment epithelium. All three patients had rod b-waves that were profoundly subnormal in amplitude and markedly delayed in implicit time to bright stimuli. Rod a-wave slopes were reduced 50% below normal, indicating photoreceptor involvement. These unusual rod ERG intensity-response functions are similar to those previously reported for the isolated cat eye with elevated retinal cyclic guanosine monophosphate (cGMP) after perfusion with isobutylmethylxanthine. This finding supports the idea that these three patients may have an elevation of retinal cGMP. Their rod ERG intensity-response functions are contrasted with those recorded from some patients with retinitis pigmentosa.

1-Methyl-3-isobutylxanthine↗
PubMed1990

Focal segmental glomerulosclerosis in a child with acute lymphoblastic leukemia.

A 13-year-old boy was found to have acute lymphoblastic leukemia 4 months after the diagnosis of nephrotic syndrome was made. Renal biopsy revealed focal segmental glomerulosclerosis (FSGS). While his leukemia remains in remission 7+ years from diagnosis, he requires chronic hemodialysis due to renal failure. The multiple immunosuppressive antileukemia agents he received did not appear to affect the progression of his renal disease.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1990

The importance of congenital hypertrophy of the retinal pigment epithelium in familial adenomatous polyposis.

We describe a family with familial adenomatous polyposis (FAP) and congenital hypertrophy of the retinal pigment epithelium (RPE). Three of five members with FAP showed flat, well-demarcated, round to oval pigmented patches of congenital hypertrophy of the RPE. We stress the importance of congenital hypertrophy of the RPE as a clinical marker in identifying patients with FAP since they are at risk for cancer.

Adenomatous Polyposis Coli↗
PubMed1990

The gap between patient reading comprehension and the readability of patient education materials.

Patient education materials and hospital forms are given to patients with little regard for their ability to read them. Nationwide sampling and data from the 1980 census suggest that a high proportion of patients cared for in public hospitals are functionally illiterate. In this study, 151 adult primary care patients in five different ambulatory care settings were tested for reading comprehension. Patient education materials and forms from each clinic were analyzed for readability using a standard computer program. A large discrepancy was found between the average patient reading comprehension and the ability levels needed to read patient education materials. The average reading comprehension of public clinic patients was 6th grade 5th month. Most tested patient education materials required a reading level of 11th to 14th grade, and standard institutional consent forms required a college-level reading comprehension. In the public clinics there was a gap of more than 5 years between patient reading levels and the comprehension levels required by written patient materials.

Adolescent↗
PubMed1990

Coccidioidomycosis: office diagnosis and treatment.

Although most patients with coccidioidomycosis are asymptomatic, up to 40 percent develop fatigue, cough, chest pain and fever. Erythema nodosum is often present. Chest radiographs may be normal or may show hilar adenopathy, infiltrates, pulmonary nodules or thin-walled cavities. The spherulin skin test is usually positive within three weeks of infection. Specific IgM [corrected] antibodies may be detected early in the course; IgG [corrected] antibodies develop after two to three months. In most patients, the disease has a self-limited course and requires no specific therapy. A few patients develop progressive pulmonary or disseminated disease. Extrapulmonary sites of disease include the skin, the skeleton and, rarely, the nervous system. Amphotericin B and ketoconazole are used to treat disseminated disease. Because coccidioidomycosis is caused by a fungus that is endemic in the Southwest, a travel history should be elicited from patients with persistent pulmonary symptoms.

Central Nervous System Diseases↗
PubMed1989

Bombesin microinfusion into the rat hypothalamic paraventricular nucleus increases blood glucose, free fatty acids and corticosterone.

Bombesin is a particularly potent hyperglycemic agent when administered intraventricularly or intracisternally in the rat. Because bombesin-like immunoreactivity is found in several forebrain regions implicated in glucoregulation, the ability of direct hypothalamic microinfusions of this peptide to affect serum metabolic fuel levels was tested. Three experiments, using anesthetized, acutely infused rats, or unanesthetized rats with chronic intracranial implants, showed that microinfusion of bombesin into the hypothalamic paraventricular nucleus caused significant, dose-related increases in serum glucose; infusions into the lateral hypothalamus or the caudate nucleus were ineffective. Infusions into the ventromedial nucleus significantly elevated glucose only in acutely anesthetized rats. In unanesthetized rats with chronic intracranial cannulae, bombesin infusions into all 3 hypothalamic sites, but not the caudate-putamen, significantly elevated blood free fatty acids, while only infusions into the paraventricular nucleus caused significant dose-related increases in blood corticosterone. The results demonstrate that the paraventricular nucleus is a sensitive site for bombesin-induced elevation of blood glucose, free fatty acids, and corticosterone. They also imply that the bombesin binding sites and immunoreactive terminals previously identified in these regions may be involved in the central regulation of circulating metabolic fuel levels and the pituitary-adrenal axis, and that the effects of acute surgery may augment the hyperglycemic response to intrahypothalamic bombesin administration.

Animals↗
PubMed1989

Schistosoma mansoni: identification and characterization of schistosomula polypeptides.

Schistosomula proteins separated by a two-dimensional (NEPHGE) gel system identify 94 major silver-stained polypeptides. When compared to polypeptides similarly separated from cercariae and adult worms; cercariae share the same polypeptides as schistosomula, adult worms share ca. 60% of the polypeptides. A group of five schistosomula polypeptides 15-31 kDa (apparent pI 8.2-8.9) was not found in adult worm extracts. To identify which polypeptides were immunogens, Western blots of the NEPHGE gels were probed with sera either from humans with chronic schistosomiasis or from mice vaccinated with irradiated cercariae. For characterization studies, polyclonal antibodies were made against the five schistosomula-specific and selected immunogenic polypeptides by immunizing mice with silver-stained spots removed from NEPHGE gels. We show that the polyclonal serum against a polypeptide of 12.5 kDa and an apparent pI of 6.70 mediated complement and eosinophil-dependent killing of schistosomula in an in vitro assay. Epitopes recognized by antibody against the 12.5-kDa polypeptide show a diffuse distribution and are found on flame cells of the excretory system of the schistosomula.

Animals↗
PubMed1989

Schistosoma mansoni tropomyosin: cDNA characterization, sequence, expression, and gene product localization.

We have defined the polypeptide pattern of 3-hr Schistosoma mansoni schistosomula on nonequilibrium two-dimensional gels (NEPHGE). An acidic group of polypeptides with a molecular weight of about 40 kDa and a pI value of around 5.0 (numbered 48/59/53) were identified as antigens on Western blots probed with chronic human infection sera or vaccinated mouse sera. Polypeptides 48/49/53 from silver-stained NEPHGE gels produced antisera that were specific as demonstrated by Western blot analysis and immunoprecipitations of in vitro translation products. A cDNA clone (clone 1) from a S. mansoni adult worm pBR322 library was isolated by using cDNA probes made from size-fractionated mRNA and defined as encoding polypeptide 49 by hybridization selection of the mRNA which was in vitro translated and immunoprecipitated with specific mouse antiserum. A lambda gt 11 expression clone which contained an insert close to the full length mRNA was isolated from a S. mansoni cercariae library. The complete sequence of the mRNA was determined by sequencing the insert of this clone as well as primer extension of total RNA. The only open reading frame coding for 284 amino acids in the 1316 nucleotide sequence showed a 44.76 to 55.44% homology with the amino acid sequences of 18 different tropomyosins from various species. Computer-predicted secondary structure of schistosome tropomyosin was mainly alpha-helix which was very similar to other tropomyosins. Northern analysis showed the mRNA to be about 1.5 kb in size and detectable at much higher levels in the adult worm stage as compared to the cercariae and the egg stages. Western blot analysis likewise showed that greater amounts of tropomyosin were detected in extracts from adult worm stage as compared to extracts from cercariae and egg stages. Immunocytochemical analysis shows that tropomyosin is strongly associated with the tegument of adult worms. The restriction digestion pattern given by genomic Southern analysis suggests the existence of introns and/or multiple gene copies. Thus polypeptide 49, an immunodominant antigen, represents schistosome tropomyosin.

Amino Acid Sequence↗