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Biomedical subjects

L R Mills

Publications and source records attributed to L R Mills.

17 recordsLinked to original sources
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

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↗
PubMed1978

Urine cytology findings in analgesic nephropathy.

Urine cytology screening for neoplasm led to the detection of 3 urothelial carcinomas and 1 severe urothelial dysplasia in 98 patients with analgesic-induced papillary necrosis. A further 18 patients had changes suggesting that they were at risk of incurring malignancy in the near future. Routine urine cytology is recommended in all cases of analgesic nephropathy.

Analgesics↗
PubMed1978

Origin of tubular complexes developing during induction of pancreatic adenocarcinoma by 7,12-dimethylbenz(a)anthracene.

Implantation of 7,12-dimethylbenz(a)anthracene (DMBA) into the pancreas of rats has been shown to induce adenocarcinoma. Complexes of tubules, which have the appearance of proliferated intralobular ducts, frequently appear during tumor development. These complexes were studied by light and electron microscopy to determine their method of formation. In addition, a tubular complex was reconstructed from serial sections to determine its three-dimensional configuration. Although tubular complexes have been thought by others to result from ductal proliferation, the following observation indicate that they originate from zymogen-granule-containing cells: a) there is a continuum of transitional stages between acini and tubules, b) most tubules decrease in size and are replaced by connective tissue (evidence of regression rather than proliferation), c) few mitotic figures are seen in tubular complexes, d) the tubules comprise many cells which have an abundance of rough endoplasmic reticulum, an organelle which is sparce in ducts, and e) the three-dimensional arrangement of tubules appears identical to the branching, anastomosing arrangement of zymogen-granule-containing cells of the normal rat pancreas. Control animals in which only sutures were placed in the pancreas showed minimal reaction. It is concluded that "acini" become recognized as tubules when loss of zymogen granules accompanies tumor induction by DMBA. Transformation of these cells could be erroneously interpreted as transformation from proliferating ducts.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1977

Immune complex glomerulonephritis associated with Klebsiella pneumoniae infection.

The kidneys of three patients who died of pneumonia due to Klebsiella pneumoniae were studied at autopsy by light and immunofluoerescent microscopy. One had no clinical evidence of renal disease; two had only microscopic hematuria and mild proteinuria. Light microscopy revealed focal proliferative glomerulonephritis in all three cases. Also in all three, immunofluorescent microscopy revealed a granular deposition of capsular polysaccharide antigens of Klebsiella pneumoniae in association with immunoglobulins and complement components in the mesangium and along the glomerular basement membrane. Furthermore, the glomerular bound immunoglobulins were eluted and demonstrated to contain antibodies specific to a capsular polysaccharide antigen of Klebsiella pneumoniae isolated from each patient. These findings may illustrate that the capsular polysaccharides of Klebsiella pneumoniae are antigenic, and that the immune complex deposition in the kidney during infection with this agent can be associated with renal morphological changes. Whether or not clinical evidence of nephritis occurs may depend on the characteristics of the infection and the host factors.

Aged↗
PubMed1976

Fine structure of pancreatic adenocarcinoma induced in rats by 7,12-dimethylbenz(a)anthracene.

We induced pancreatic adenocarcinomas in Long-Evans rats by placing crystals, 2-3 mg, of 7,12-dimethylbenz[a]anthracene (DMBA) in a 2- to 3-mm incision in the "head" of the pancreas approximately 1 cm from the duodenum. The incisions were closed with one or two silk sutures. The animals were killed 4-10 months after DMBA implantation, and nodules were removed and routinely prepared for light and/or electron microscopic study. Histologic organization varied from normal, through areas of tubule-like structures, to sheets of pleomorphic tumor cells. Electron microscopic study of tumor cells revealed large electron-lucent nuclei that frequently had irregular outlines and prominent nucleoli. The predominant feature of the cytoplasm was abundant rough endoplasmic reticulum. Zymogen granules were rare. Adjacent cells sometimes were jointed by an apical junctional complex to form a lumen into which projected irregular microvilli. A basal lamina sometimes occurred at the bases of the tumor cells. The fine structural similarity of these tumor cells to acinar cells was noted.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1975

Experimental induction of pancreatic adenocarcinoma in rats.

Adenocarcinomas of the pancreas were experimentally induced in rats after the implantation of 7,12-dimethylbenz[alpha]anthracene (DMBA). Rats were anesthetized with Nembutal, the pancreas was exposed, and a 2- to 3-mm incision was made in the "head" of the pancreas approximately 1 cm from the duodenum. Crystalline DMBA (2-3 mg) was implanted and the incision was closed with silk suture. Eight % of animals developed tumors in the pancreas from 119 to 363 days after implantation (mean, 194 days). Ten animals developed tumors in less than 180 days. The adenocarcinomas were invasive, metastasized, and had pronounced ductal cell characteristics. The light-microscopic morphology of these pancreatic tumors was presented.

9,10-Dimethyl-1,2-benzanthracene↗