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Biomedical subjects

J Wells

Publications and source records attributed to J Wells.

At least 163 records · Page 9Linked to original sources

Cross-species septal transplants: recovery of choline acetyltransferase activity.

Following interruption of the fornix-fimbria pathway, hippocampal choline acetyltransferase (ChAT) activity was restored gradually by cross-species cell suspension transplants of embryonic septum. The hippocampal segment closest to the implant reached 35% of normal 17 weeks after transplantation. The overall restoration of ChAT by xenogenic cell suspension had many similarities to that reported for homogenic solid and cell suspension septal grafts. The time course of the recovery of ChAT activity was different from the time course of the ingrowth of acetylcholinesterase stained fibers reported previously.

Animals↗

The influence of the hair cycle on the thickness of mouse skin.

The data on mouse skin thickness reported here was prompted by the need to know the true position of basal cells of the epidermis and hair follicles as these are important "cells at risk" for a variety of skin reactions including carcinogenesis following exposure to radiation. There is little reliable data in the literature and most previous reports have ignored the shrinkage of skin that occurs because of its natural elasticity. The values determined for mouse flank skin in telogen--the resting phase of the hair cycle for the different skin layers--are epidermis 10 micron, corium 250 micron, adipose layer 150 micron, and hair follicle depth 150 micron. Three days after chemical depilation which triggers the hair follicles into active cycle (anagen) the epidermis doubles in thickness, remains at this value for 7 days, and then gradually returns to telogen values by day 18. The corium and adipose layers also increase significantly to reach approximately 390 micron and approximately 260 micron, respectively, by day 10 and then return to control values from day 15 onward. The change in hair follicles depths are more dramatic with active follicle basal cells reaching approximately 450-550 micron into the adipose layer between days 7 and 15. One important finding is that chemical depilation does not affect the telogen thickness of skin-the teleogen values for the epidermis and dermis immediately prior to and immediately after depilation were similar to those 23 days later at the beginning of the next telogen phase.

Animals↗

Changes in the DNA labelling index after beta irradiation of the mouse epidermis.

This study looked at the changes in the interfollicular DNA labelling index (LI) with time after strontium-90/yttrium-90 beta irradiation of approximately 100 mm2 of mouse flank skin, after a dose of 100 Gy which produces transitory moist desquamation. Within 24 hr of such a dose the LI of the irradiated area was essentially zero (0.07 +/- 0.03%), whilst those of the side area and of the control area were 15.0 +/- 2.6% and 21.4 +/- 2.7%, respectively. The LI of the side and the control areas then fell within 3-5 days to approximately 4% and approximately 2% respectively, whilst that of the irradiated area rose rapidly to a peak value of 30.2 +/- 1.7% at 10 days post-irradiation. There was a 20% reduction in the diameter of the area with detectable radiation damage within 5 days, and this is primarily due to cell proliferation and migration from the unirradiated margins of the field. In contrast, between days 10 and 20 the major source of repopulation is probably derived from local migration and proliferation of surviving hair follicle basal cells within the irradiated field.

Animals↗

Nonstochastic effects of different energy beta emitters on the mouse skin.

The effect of irradiating varying areas of mouse skin from 860 down to 0.8 mm2 with different energy beta emitters was studied to clarify protection problems of localized doses to the skin. Both 90Sr and 170Tm sources show area effects for dose-response curves. The 90Sr doses that produced moist desquamation in 50% of irradiated fields (MD-50 doses) were 22, 42, 70, and 1000 Gy for 400-, 95-, 20-, and 0.8-mm2 sources. The MD-50 doses for 170Tm were 50, 54, 90, and 170 Gy for 860-, 64-, 20-, and 3.1-mm2 sources. Thus for the larger 170Tm sources there is much less area effect. There was no significant difference in effect between the different energy 90Sr and 170Tm sources for moist desquamation. A simple hypothesis based upon the repopulation of epithelial cells from the edges of the irradiated field and/or from surviving follicle basal cells can explain these area and energy effects in the mouse and in parallel pig skin experiments. The doses needed for 50% of the mice to show ulceration after 64-, 20-, and 3.1-mm2 170Tm sources were 260, 550, and 8300 Gy, respectively, while those for 90-, 20-, and 0.8-mm2 90Sr sources were 150, 210, and 3100 Gy. Thus there is a definite area and energy effect for these sources for this deep dermal damage. The steep rise in dose needed to produce given skin reactions for the smallest area (0.8 mm2) should reassure those faced with assessing the hazard of sub-millimeter-sized particles in/on human skin.

Animals↗

Nonstochastic effects of different energy beta emitters on pig skin.

Circular areas of pig skin from 1- to 40-mm diameter were irradiated with beta emitters of high, medium, and low energies, 90Sr, 170Tm, and 147Pm, respectively. The study provides information for radiological protection problems of localized skin exposures. During the first 16 weeks after irradiation 90Sr produced a first reaction due to epithelial cell death followed by a second reaction attributable to damage to the dermal blood vessels. 170Tm and 147Pm produced the epithelial reaction only. The epithelial dose response varied as a function of beta energy. The doses required to produce moist desquamation in 50% of 15- to 22.5-mm fields (ED50) were 30-45 Gy from 90Sr, approximately 80 Gy from 170Tm, and approximately 500 Gy from 147Pm. A model involving different methods of epithelial repopulation is proposed to explain this finding. An area effect was observed in the epithelial response to 90Sr irradiation. The ED50 for moist desquamation ranged from approximately 25 Gy for a 40-mm source to approximately 450 Gy for a 1-mm source. The 5-, 9-, and 19-mm 170Tm sources all produced an ED50 of approximately 80 Gy, while the value for the 2-mm source was approximately 250 Gy. It is also suggested that the area effects could be explained by different modes of epithelial repopulation after irradiation. After high energy beta irradiation repopulation would be mainly from the field periphery, while after lower energy irradiation repopulation from hair follicle epithelium would predominate.

Animals↗

Genetic transfer of antimicrobial resistance and enterotoxigenicity among Escherichia coli strains.

To understand the role of enterotoxin (Ent) plasmids in epidemics of enterotoxigenic (ET) Escherichia coli diarrhea in the United States, we studied the genetics of Ent plasmids in relation to E. coli serotypes and R plasmids. Twenty-nine ET E. coli strains, including all epidemic isolates available at the Centers for Disease Control, Atlanta, Ga. (CDC), were assessed for the ability to transfer antimicrobial resistances (if present) by conjugation, to mobilize a nonconjugative R plasmid, and to cotransfer enterotoxigenicity with R determinants. Of the 12 ET E. coli strains isolated in the United States, 5 were able to transfer R plasmids; one strain cotransferred detectable enterotoxigenicity. Another four U.S. isolates were able to mobilize plasmid DNA, but no toxin production was detected in transconjugants. Of 17 resistant ET E. coli from South Asia, 13 were able to transfer R plasmids; 5 of those 13 cotransferred detectable Ent plasmids. In all, 22 ET E. coli strains (76%) were able to initiate conjugation and genetic transfers. Six of these strains (20%) were able to cotransfer enterotoxigenicity with a conjugative R plasmid at a detectable frequency. One of the six strains transferred R and Ent determinants on a single plasmid. These data are addressed in relation to the observed immobility of Ent and R during outbreaks of ET E. coli, the efficacy of prophylactic tetracycline, and the worldwide occurrence of a limited number of ET E. coli serotypes.

Conjugation, Genetic↗

Synaptic arrangements in the ventral posterolateral nucleus of the squirrel.

Because murine rodents have no complex synaptic arrangements in the ventral posterolateral nucleus (VPL), we sought to determine if the lack of complexity was a characteristic common to all rodents. We studied the synaptology of VPL in the fox squirrel, Sciurus niger, using electron microscopy. We found vesicle-containing dendrites and complex synaptic arrangements in the squirrel VPL. Therefore, the relative simplicity of the rat and mouse VPL is not a general feature of the rodent somatosensory thalamus.

Animals↗

Tumor markers in inclusion cysts of the ovary.

The immunoperoxidase method was used to determine whether carcinoembryonic antigen, beta subunit of HCG placental lactogen, pregnancy-associated alpha-2 glycoprotein, and pregnancy-specific beta-1 glycoprotein could be found in inclusion cysts of the ovary. These tumor markers are found in the serum of patients with common epithelial carcinomas of the ovary and inclusion cysts are considered to be the origin of these tumors. Placental lactogen was found in 56 of 118 inclusion cysts, beta subunit of HCG in four of 141 cysts, alpha-2 glycoprotein in five of 141, and beta-1 glycoprotein in two of 118. it was concluded that primitive cells in inclusion cysts elaborate the same tumor markers found in serous cystadenoma and cystadenocarcinoma of the ovary. This observation, although not proving origin of tumor from the inclusion cyst, demonstrates a significant characteristic shared in common by all three.

Carcinoembryonic Antigen↗

The development of cerebellar primordia transplanted to the neocortex of the rat.

Pieces of cerebellar primordia were dissected from the developing fetus at day 18 of gestation in Sprague-Dawley rats and transplanted to the neocortex of a 10- to 12-day-old rat. The histological development of 53 such transplants was analyzed at a series of survival times ranging from 5 min to 426 days. The cerebellar cortex developed much as it does in situ. However, only migratory sequences were strictly followed, while Purkinje cell differentiation and folia formation were initially retarded. In deep parts of the transplant, and throughout transplants confined to deep layers of the neocortex, the external granule layer was associated with penetrating blood vessels. An inverted cytoarchitectural pattern developed as concentric cylindrical layers around these vessels. In contrast, normal lamination and foliation were found only in transplants growing on the neocortical surface. Axons coursing between host and transplant were seen frequently and were especially pronounced at those sites beneath the internal granule layer which appeared to contain deep cerebellar nuclei. At the longest survival time there was preliminary evidence that suggested morphological deterioration of the transplant. Surface transplants, in addition to developing a normal orientation of cells and layers, have the added benefit of being accessible for further experimental manipulations after the transplant has become established.

Animals↗

Analysis of histone gene expression during the cell cycle in HeLa cells by using cloned human histone genes.

Although it is generally agreed that histone protein synthesis is restricted to the S phase of the cell cycle--and therefore parallels DNA replication--both transcriptional and posttranscriptional levels of control have been invoked. Using blot hybridization with several cloned genomic human histone sequences representing different histone gene clusters as probes, we have assessed the steady-state level of histone RNAs in the nucleus and cytoplasm of G1 and S phase HeLa S3 cells. The representation of histone mRNA sequences of G1 compared with S phase cells was less than 1% in the cytoplasm and approximately 1% in the nucleus. These data are consistent with transcriptional control, but we cannot completely dismiss the possibility that regulation of histone gene expression is, to some extent, mediated posttranscriptionally. If histone gene transcription does occur in G1, the RNAs must either be rapidly degraded or be transcribed to a limited extent compared with S phase. An unexpected result was obtained when a blot of cytoplasmic RNA from G1 and S phase cells was hybridized with lambda HHG 41 DNA (containing H3 and H4 human genomic histone sequences). Although hybridization with histone mRNAs was observed for RNAs from S phase but not from G1 cells, hybridization with a nonhistone RNA of approximately 330 nucleotides present predominantly in G1 was also observed.

Bacteriophage lambda↗

Organization of human histone genes.

We describe the isolation and initial characterization of seven independent lambda Charon 4A recombinant phages which contain human histone genomic sequences (designated lambda HHG). Restriction maps of these clones and localization of the genes coding for histones H2A, H2B, H3, and H4 are presented. The presence of histone encoding regions in the lambda HHG clones was demonstrated by several independent criteria including hybridization with specific DNA probes, hybrid selection/in vitro translation, and hybridization of lambda HHG DNAs to reserve Southern blots containing cytoplasmic RNAs from G1-, S-, and arabinofuranosylcytosine (cytosine arabinoside)-treated S-phase cells. In addition, the lambda HHG DNAs were shown to protect in vivo labeled H4 mRNAs from S1 nuclease digestion. Based on the analysis of the lambda HHG clones, human histone genes appear to be clustered in the genome. However, gene clusters do not seem to be present in identical tandem repeats. The lambda HHG clones described in this report fall into at least three distinct types of arrangement. One of these arrangements contains two coding regions for each of the histones H3 and H4. The arrangement of histone genes in the human genome, therefore, appears to be different from that in the sea urchin and Drosophila genomes in which each of the five histone-encoding regions (H1, H2A, H2B, H3, and H4) is present only once in each tandemly repeated cluster. At least one clone, lambda HHG 41, contains, in addition to the histone genes, a region that hybridizes with a cytoplasmic RNA approximately 330 nucleotides in length. This RNA is not similar in size to known histone-encoding RNAs and is present in the cytoplasm of HeLa cells predominantly in the G1 phase of the cell cycle.

Bacteriophage lambda↗

Monoclonal and heteroantibody reacting with different antigens common to human blast cells and monocytes.

A mouse monoclonal antibody CBL1 and a rabbit heteroantisera 157 raised to a lymphoblastoid T ALL cell line, CEM, appear to be specific for blast cells. Both CBL1 and 157 reacted with all PHA blasts and lymphoblastoid cell lines and the majority of leukemic blast cells tested. From serological reactivity and immunoprecipation experiments, CBL1 and 157 appeared to detect different blast cell antigens. There were leukemia blast cells from six patients that gave a different reaction pattern with CBL1 and 157. Antiserum 157 immunoprecipitated a 90,000 dalton antigen under reducing conditions which appeared as a 180,000 dalton disulfide-linked dimer under nonreducing conditions. Immunoprecipitation with CBL1 using the same 125I-labeled cell lysates gave no observable antigenic peaks.

Antibodies↗

Inclusions in ovaries of females aged day 1-30 years.

This study was an examination of ovaries in the age group day 1-30 years. One hundred eight cystic epithelial inclusions cysts were found in 40 ovaries in the age group of day 1-7 years. All were lined by cuboidal and low columnar epithelium. A total of 81 cystic epithelial inclusions were found in 58 ovaries in individuals aged 12-30 years. Thirty four were lined by endosalpingeal cells, reflecting metaplasia of the epithelium. Metaplasia may be induced hormonally as none of the inclusions in premenarchal ovaries showed similar changes. In two cases in which an ectopic pregnancy was present in the fallopian tube, inclusions were lined by cells resembling those described by Arias-Stella, further strengthening the view that surface epithelium covering the ovary and lining cystic epithelial inclusions is responsive hormonally.

Adolescent↗