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L R Mills

Publications and source records attributed to L R Mills.

At least 37 records · Page 2Linked to original sources
PubMed1994

N-type Ca2+ channels are located on somata, dendrites, and a subpopulation of dendritic spines on live hippocampal pyramidal neurons.

In the nervous system the influx of Ca2+ orchestrates multiple biochemical and electrical events essential for development and function. A major route for Ca2+ entry is through voltage-dependent calcium channels (VDCCs). It is becoming increasingly clear that the precise contribution VDCCs make to neuronal function depends not only upon their specific electrophysiological properties but also on their distribution over the nerve cell surface. One location where the presence of VDCCs may be critical is the dendritic spine, a structure known to be the major site of excitatory synaptic input. On spines, VDCCs are hypothesized to play an essential role in signal processing, learning, and memory. However, direct evidence for the presence of VDCCs on spines is lacking. Attempts to examine the distribution of VDCCs, or indeed any other components, on spines have been hampered since the size of many spines is close to the limits of resolution of conventional light microscopy. Using a new, biologically active, fluorescein conjugate of omega-conotoxin (Fl-omega-CgTx), a selective blocker of N-type VDCCs, and confocal microscopy, we have mapped the distributions of N-type VDCCs on live CA1 neurons in rat hippocampal slices. VDCCs were found on somata, throughout the dendritic arbor, and on dendritic spines in all hippocampal subfields. A comparison of three-dimensional reconstructions of structures labeled by Fl-omega-CgTx with those outlined by 1,1-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine (Dil) or Lucifer yellow confirmed the presence of N-type VDCCs on dendritic spines. However, spine frequency on dendrites labeled with Fl-omega-CgTx was much lower than the spine frequency on dendrites labeled with Lucifer yellow or Dil, suggesting that some spines lack N-type VDCCs. These results offer the first direct evidence for the localization of any voltage-dependent channel on dendritic spines. The presence of N-type VDCCs on dendrites and their spines argues that these channels may participate in the generation of active Ca2+ conductances in distal dendrites, and is consistent with a role for spines as specialized compartments for concentrating Ca2+.

Animals↗
PubMed1994

Crohn's disease of the esophagus.

We report a case of Crohn's esophagitis involving the entire intrathoracic esophagus, and without evidence of inflammatory bowel disease elsewhere, that was treated successfully with esophagectomy. The clinicopathologic features and the literature are reviewed.

Crohn Disease↗
PubMed1993

Lymphocytic colitis. A definable clinical and histological diagnosis.

We reviewed colorectal biopsies and clinical records from 36 patients with chronic watery diarrhea who had been diagnosed as having microscopic colitis and compared their histologic features with the more detailed and precise criteria for lymphocytic colitis. Published pathologic criteria for lymphocytic colitis were applied to the biopsies and compared. Focal or diffuse nature of the lymphoid infiltrate were noted separately. The focal lymphoid infiltrate was related to lymphoid aggregates in the lamina propria of the mucosa. Eighteen cases had focal lymphoid cell infiltration, and 16 of them had associated diverticula, polyps, or both. Eighteen cases had diffuse lymphoid cell infiltration, and six of them had diverticula or polyps. Results indicate that focal cellular infiltration strongly predicts associated diverticula or polyps. The group with no diverticula or polyps most closely conformed to histologic criteria for lymphocytic colitis (Kruskal-Wallis P < 0.02). We conclude that lymphocytic colitis comprises a well-defined group of cases within the large and less-defined group of microscopic colitis.

Adult↗
PubMed1992

Effects of serotonin on intracellular calcium in embryonic and adult Helisoma neurons.

The neurotransmitter serotonin has been shown to regulate neurite outgrowth in many embryonic and adult Helisoma neurons. To determine whether intracellular calcium concentration is also regulated by serotonin in large numbers of neurons, the calcium indicator Fura 2 was used to measure intracellular calcium in mass-dissociated cultures of embryonic and adult neurons. Comparisons between embryonic and adult neurons revealed that embryonic neurons have a narrow population distribution of rest intracellular calcium levels around relatively low values. In contrast, the population distribution for adult neurons covered a much wider range of rest calcium concentrations. In both embryonic and adult cultures, serotonin induced a shift in the population distribution of calcium concentrations to higher levels, and increased the mean and median calcium concentrations. Analysis of individual adult neurons prior to and following the addition of serotonin revealed that approximately 50% of the neurons responded with an increase in calcium concentration. In contrast, there was no evidence of a serotonin-induced decrease in calcium concentration in any neurons. Since the percentage of neurons responding to serotonin in this study is very similar to the percentage that responded in previous studies on neurite outgrowth, these data support the hypothesis that an increase in intracellular calcium is a common intermediate step in the regulation of neurite outgrowth by serotonin throughout the Helisoma nervous system.

Animals↗
PubMed1992

Colon polyps.

Colonic polyps commonly occur in all age groups and are of varied significance depending on the type of polyp and the symptoms manifested. There is some debate in the medical literature regarding the appropriate clinical management of polyps and the follow-up of patients after polypectomy. This discussion addresses the significance of colon polyps, including their etiology, histology, complications, detection, and management.

Adenoma↗
PubMed1991

Novel effects of serotonin on neurite outgrowth in neurons cultured from embryos of Helisoma trivolvis.

The neurotransmitter serotonin has been shown to inhibit neurite outgrowth in specific identified neurons isolated from adult Helisoma. While in vivo experiments on Helisoma embryos have supported the hypothesis that endogenous serotonin regulates neurite outgrowth during embryonic development, direct effects of serotonin on embryonic neurons have not been measured. In the present study, cultures of dissociated embryonic neurons were used to test the direct actions of serotonin on developing embryonic neurons. Serotonin arrested neurite outgrowth in a significant percentage of elongating neurites in a dose-dependent manner. Furthermore, analysis of neurons with stable, nonelongating neurites revealed a novel response. Serotonin caused the reinitiation of neurite outgrowth in a significant percentage of nonelongating neurites. The arrestment of outgrowth and reinitiation of outgrowth occurred in similar percentages of elongating and nonelongating neurites, respectively. Parallel experiments on cultures of dissociated adult neurons were carried out to determine whether serotonin could also induce both inhibitory and stimulatory responses in adult cells. Serotonin arrested neurite outgrowth in a similar percentage of neurites to that observed in cultures of embryonic neurons. In contrast, serotonin did not reinitiate neurite outgrowth in a significant percentage of adult neurites. These data support the hypothesis that serotonin regulates neurite outgrowth in developing embryonic neurons. Furthermore, only some of these regulatory effects appear to be conserved from embryonic to adult neurons.

Aging↗
PubMed1991

Differential expression of c-myc and H-ras oncogenes in Barrett's epithelium. A study using colorimetric in situ hybridization.

To determine the role of c-myc and H-ras in progressive, dysplastic Barrett's mucosa (BM), and the usefulness of these oncogenes as markers for dysplastic lesions at high risk for malignant transformation, sequential formaldehyde solution-fixed, paraffin-embedded biopsy specimens that were obtained from 12 patients with BM were evaluated by in situ hybridization with the use of biotinylated complimentary DNA probes. Nine of the patients were taken from a previous prospective study. Four of these nine patients had dysplasia, and adenocarcinoma had developed in two of them; five had nondysplastic BM only. Two additional patients had adenocarcinoma, but their initial biopsy specimens had revealed dysplasia. One additional patient had intermediate-grade dysplasia. The intensity of oncogene expression was quantified by computerized color-image analysis. Enhanced c-myc expression of approximately equal intensity was consistently observed in all grades of dysplasia and carcinoma. H-ras was also consistently expressed in higher grades of dysplasia and carcinoma but not in low-grade dysplasia. Neither c-myc nor H-ras expression was detected in nondysplastic BM. The expression of H-ras in dysplastic BM appears to be a helpful marker for identifying which dysplastic lesions will progress to carcinoma.

Chronic Disease↗
PubMed1990

Neuron-specific modulation by serotonin of regenerative outgrowth and intracellular calcium within the CNS of Helisoma trivolvis.

We have investigated the cell-specific effect of serotonin (5-HT) on regenerating neurons within the adult central nervous system of the pond snail, Helisoma trivolvis. In culture, 5-HT arrests outgrowth of buccal neurons B19 but not neurons B5 (Haydon, McCobb, and Kater, 1984). After axotomy, neurons within the Helisoma nervous system typically exhibit profuse regenerative outgrowth. This study, on neurons within the CNS, shows that 5-HT selectively inhibits the outgrowth of specific identified neurons, and also causes significant elevations in intracellular calcium concentrations as measured by the calcium indicator dye, Fura-2. The outgrowth of neurons B19 and C1 was selectively inhibited when ganglia were incubated in 5 X 10(-5) M 5-HT. The outgrowth of buccal neurons B5, however, was not affected. Moreover, 5-HT caused significant transient elevations of calcium concentrations in neurons B19 over 30 minutes, but neurons B5 did not show any increases in calcium concentrations with the addition of 5-HT. These results suggest that the effect of 5-HT upon outgrowth of regenerating neurons may be due to an increase in the intracellular calcium concentration.

Animals↗
PubMed1990

Neurotransmitter activation of second messenger pathways for the control of growth cone behaviors.

The generation and regeneration of neuronal form and connectivity both undoubtedly rely upon the integration of intrinsic and extrinsic information of many kinds. Our work has demonstrated that the concentration and spatial distribution of intracellular calcium is a key locus of integration of such information. Through a delicate balance of mechanisms that raise free calcium and mechanisms that lower free calcium, a steady state level is achieved that appears to have significant regulatory control over neuronal growth cone behavior. Cues, both internal and external, alter intracellular calcium levels, and consequently alter growth cone behavior. It is through the alteration of the various components of calcium homeostasis that we envision the complexities of neuronal architecture and connectivity may be fine-tuned throughout the life histories of neuronal ensembles.

Animals↗
PubMed1990

Neuron-specific and state-specific differences in calcium homeostasis regulate the generation and degeneration of neuronal architecture.

Many stimuli (e.g., neurotransmitters and electrical activity) regulate neuromorphogenesis by changing intracellular calcium. The ionophore A23187 was employed as a receptor-independent method to investigate neuronal calcium homeostasis. Distinctive neuron-specific (B5 versus B19) and state-specific (growing versus non-growing) differences in calcium homeostasis were observed in cultured identified Helisoma neurons. Fura-2 studies revealed that A23187 induced a transient rise in intracellular calcium in growing neurons B5 but a sustained rise in growing neurons B19. In stable-state (non-growing) cells A23187 evoked only a transient calcium rise. Both neuron-specific and state-specific differences in calcium homeostasis were dependent on extracellular sodium. Morphological studies also indicated that such differences in calcium-regulatory capacity can have profound consequences on the generation and degeneration of neuronal architecture.

Animals↗
PubMed1989

The neural dependency of Merkel cell development in the rat: the touch domes and foot pads contrasted.

We have used the quinacrine labeling technique and electron microscopy to study the development of the Merkel cell population in the skin of the rat and how this is affected by denervation produced at birth and at various times thereafter. An unexpected difference was found between the Merkel cells of glabrous and hairy skin. In the paw pads of rats aged 1 day or older the Merkel cells differentiated normally and survived quantitatively in the absence of their nerves. In the touch domes however, denervation at 1-4 days prevented the differentiation of the normal Merkel cell population and led to the disappearance of all or most of the Merkel cells that were already present. The Merkel cells in touch domes of the lower leg were affected by denervation like those of the back skin, differing strikingly from the Merkel cells of the footpads, even though the hairy skin of the leg and the glabrous skin of the foot are innervated by the same anatomical nerve. In adult rats, axons regenerating to denervated paws reinnervated epidermal Merkel cells of the pads and restored essentially normal mechanosensitivity to them; thus the Merkel cells of mammalian glabrous skin, like their counterparts in the wholly glabrous skin of lower vertebrates (S. A. Scott, E. Cooper, and J. Diamond, 1981, Proc. R. Soc. London B211, 455-470; K. M. Mearow and J. Diamond, 1988, Neuroscience 26, 695-708), can act as targets for ingrowing nerves. However, even though the differentiation of Merkel cells in hairy skin is nerve dependent, they probably have in common with the Merkel cells of glabrous skin the role of acting as final targets for nerves during development and regeneration.

Aging↗
PubMed1989

Scanning electron microscopy of dysplastic Barrett's epithelium.

Twenty-six patients with Barrett's esophagus (BE) were followed prospectively by endoscopic examination and biopsy. Two biopsies were taken from each of 4 areas of BE. One was processed for light microscopy (LM) and one for scanning electron microscopy (SEM). Those in whom dysplastic BE was demonstrated by LM were reexamined at 6-mo intervals, and the others at yearly intervals. One patient had low grade dysplasia (LGD) by LM on entry, and in 2 others, LGD was recognized on the second examination. These changes have persisted in semiannual examinations over 3, 2, and 2 yr, respectively. SEM prints were examined without knowledge of LM findings, and features that might correlate with LGD by LM were sought. SEM findings were similar to those of Zwas et al. (Gastroenterology 90:1932, 1986) in that most glandular cells had surface features unlike either gastric or intestinal cells but unique to BE. In the patient with LGD on entry, there was an aggregate of very large cells covered by short microvilli with bald patches. In the other patients with LGD, there was more variation in size and shape of cells than in nondysplastic cases.

Adult↗
PubMed1988

Recovery from hepatic vein thrombosis (Budd-Chiari syndrome) complicating ulcerative colitis.

A 22-year-old female with active ulcerative colitis developed massive ascites, hypoalbuminemia, and hepatomegaly compatible with thrombosis of the hepatic veins. The diagnosis of Budd-Chiari syndrome was confirmed by ultrasonography, computed tomography, and by liver biopsy. A search of the literature disclosed only three previous reports of Budd-Chiari syndrome occurring in patients with ulcerative colitis. All patients have been young females with active colitis and no other known risk factor for the development of hepatic vein thrombosis. Our patient, unlike the previously reported patients who died, recovered sufficiently to be discharged from the hospital.

Adult↗
PubMed1988

Early effects of ionizing radiation on pulmonary endothelial angiotensin-converting enzyme and 5'-nucleotidase, in vivo.

We investigated the early phase of pulmonary endothelial injury in rabbits exposed to a single dose (30 Gy) of ionizing radiation to the chest, by measuring endothelium-bound ectoenzyme activities. Utilizing multiple indicator-dilution techniques, the metabolism of [3H]benzoyl-Phe-Ala-Pro (BPAP) and [14C]5'-AMP by angiotensin-converting enzyme (ACE) and 5'-nucleotidase (NCT), respectively, was studied during a single transpulmonary passage in conscious, chronically catheterized rabbits. From these data, the apparent kinetic constants Km and Amax were calculated. A significant (p less than 0.05) decrease in the metabolism of trace amounts of BPAP and 5'-AMP was observed at 2, 24, and 48 hr after irradiation. A similar decrease in the apparent first order rate constant (Amax/Km) of ACE was observed at 2 hr, but returned to control levels by 24 and 48 hr after irradiation. Apparent Km values of ACE for BPAP and NCT for 5'-AMP were elevated at 2, 24, and 48 hr post-treatment, whereas Amax (product of enzyme mass and the constant of product formation, kcat) of ACE was elevated at 2 and 24 hr but not at 48 hr, and Amax for NCT was elevated at 2 hr post-treatment only. Significant decreases in mean arterial blood pressure and pulmonary blood flow (Qb) at 2 hr post-treatment, and increases in Qb at 24 and 48 hr post-treatment were also recorded. No changes in endothelial structure were observed 2 hr after irradiation at the light or electron microscope level. We conclude that the early phase of radiation-induced lung injury includes changes in endothelial enzyme function in the absence of structural damage, as reflected in an apparent decrease in affinity of ACE and NCT for their substrates, allowing for the possibility that hemodynamic disturbances or their sequalae could also have contributed to the decrease in enzyme function.

5'-Nucleotidase↗