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M H Johnson

Publications and source records attributed to M H Johnson.

At least 55 records · Page 3Linked to original sources
PubMed2000

Characterization of Ly-6M, a novel member of the Ly-6 family of hematopoietic proteins.

The Ly-6 family includes a number of highly homologous, low molecular weight glycophosphatidylinositol-linked proteins expressed on hematopoietic and lymphoid cells. The best characterized family member is Sca-1 (Ly-6A/E), an antigen commonly used for purification of murine pluripotent hematopoietic cells. We sought to characterize the genomic locus surrounding the Sca-1 gene. We identified several overlapping P1 artificial chromosomes containing the Sca-1 gene and mapped one of these to mouse chromosome 15D3.1-3.3, the region previously shown to contain members of the murine Ly-6 gene family. We then mapped this clone and found that the Sca-2 gene lies 35.4 kilobase (kb) downstream of Sca-1 in the opposite transcriptional orientation. This is the first direct demonstration of physical linkage of Ly-6 genes. A novel gene, highly homologous to Sca-1 was identified and localized 13.4 kb downstream of Sca-1. This gene, which we designated Ly-6M, shares several structural features conserved among members of the Ly-6 family. Ly-6M messenger RNA (mRNA) is easily detectable in hematopoietic tissue (bone marrow, spleen, thymus, peritoneal macrophages) as well as kidney and lung. No mRNA expression was detected in heart, stomach, liver, small intestine, brain, or skin. Ly-6M protein is detectable on 10% to 15% of peripheral blood leukocytes, including monocytes and a subpopulation of B220(+) cells. Ly-6M is broadly distributed in the bone marrow, with prominent expression on monocytes and myeloid precursors. The identification and characterization of Ly-6M adds a new member to a complex family of homologous, tightly linked genes that have proven extremely useful reagents for defining populations within the hematopoietic system.

Amino Acid Sequence↗
PubMed2000

Cortical development and saccade planning: the ontogeny of the spike potential.

The spike potential is a sharply timed positivity which precedes eye movements in adults, and is thought to indicate cortical planning of saccades. While the spike potential is observed under most conditions in adults, it has not been reported in young infants. In the present study we shed light on the ontogeny of the spike potential by demonstrating for the first time its existence in a group of older infants (12 months). This result is consistent with a relatively delayed onset of cortical control over saccades during development.

Age Factors↗
PubMed2000

Antitumor activity of mifepristone in the human LNCaP, LNCaP-C4, and LNCaP-C4-2 prostate cancer models in nude mice.

BACKGROUND: Antiprogestins are a promising new class of mammary tumor inhibitors with a unique mechanism of action. Previously published results also suggest a tumor-inhibitory effect of antiprogestins in prostate cancer models. The objective of the present studies was to determine whether androgen-sensitive and androgen-insensitive variants of the well-characterized LNCaP human prostate cancer cell line exhibit stable differences in their sensitivity to in vivo antitumor activity of the antiprogestin, mifepristone. METHODS: Exponentially growing LNCaP, LNCaP-C4, and LNCaP-C4-2 prostate cancer cells in culture were mixed with Matrigel and injected subcutaneously (s.c.) into the flank of 6-8-week-old male nude mice. The tumors were permitted to grow until they reached a volume of 270-300 mm(3). The animals were then randomly assigned to two groups. One group received mifepristone (50 mg/kg/day s.c.). Control animals were treated with vehicle. Tumor volume was determined every 4 days. After 28 days of treatment, the tumors were harvested and wet weights were determined. RESULTS: The inoculated tumor cells produced progressively growing tumors in male nude mice. However, the androgen-insensitive LNCaP-C4-2 cells showed the most aggressive and most rapid growth rate and shortest time to tumor progression. The tumors derived from the LNCaP-C4 cells exhibited a higher rate of tumor growth as compared with those derived from the parental androgen-sensitive LNCaP cells. In all three models, mifepristone treatment caused a significant retardation of tumor progression: after 28 days of treatment, about 50% inhibition of tumor weight was observed in the mifepristone treatment groups (P < 0.05) compared with the corresponding control groups. CONCLUSIONS: This is the first report demonstrating significant antitumor activity of mifepristone in both androgen-sensitive and androgen-insensitive variants of the LNCaP human prostate cancer model in nude mice. These results suggest a potential clinical benefit of the use of antiprogestins as a novel nonandrogen ablation therapeutic approach in the management of prostate cancer.

Androgens↗
PubMed2000

Egg timers: how is developmental time measured in the early vertebrate embryo?

Eggs and early embryos appear to be programmed to undertake particular developmental decisions at characteristic times, although precisely how these decisions are timed is unknown. We discuss the possible roles and interactions during early vertebrate development of two broad categories of timers: 1) those that involve cyclic or sequential mechanisms, referred to as clocks; and 2) those that require an increase or decrease in some factor to a threshold level for progression of time, referred to as hourglass timers. It is concluded that both clock-like timers linked to various features of the cell cycle and hourglass timers are involved in early developmental timing. The possible involvement of elements of circadian clock timers is also considered. BioEssays 22:57-63, 2000.

Animals↗
PubMed2000

Electrophysiological correlates of category goodness.

We report the results obtained from a behavioural and electrophysiological study. A synthesised continuum going from labial /ba/ to retroflex /da/ through dental /da/ was tested for category goodness. Native English speakers rated different tokens from each category as good, bad or ambiguous. The results showed that not all of the representatives of each category were ideal and that the categories tested have an internal structure. The electrophysiological study evaluated whether event related potentials (ERPs) mirrored the goodness judgements. During a passive oddball task, the same participants were exposed to native /ba/-/da/, Hindi dental /da/-retroflex /da/ and within-category /ba/-/ba/ contrasts. Results showed that participants pre-attentively perceive the differences in all cases, as shown by mis-match negativities (MMN), late positive deflections (LPD) or greater N1 and/or P2 components for deviant stimuli. Acoustic sensitivities, categorical perception and category goodness all contributed to the waveforms obtained. We attribute the ERP effects to a combination of (1) prototypes built from initial sensitivities, (2) reinforcement with exposure to one's native language and (3) no permanent loss of the initial boundaries explains the effects observed.

Adult↗
PubMed2000

Regulation of fertilization-induced Ca(2+)spiking in the mouse zygote.

Fertilization-induced Ca(2+)spiking in mouse zygotes ceases at the end of pre-G1 as pronuclei (PN) form. In the present studies we found that there was no consistent temporal relationship between PN formation and cessation of spiking. We also show that nucleate and anucleate fragments of zygotes, obtained by bisection of fertilized eggs prior to PN formation, both ceased spiking at times that did not depend on the presence of the PN. We, therefore, concluded that formation of the PN does not cause spiking cessation. The possibility that cessation of the fertilization-induced Ca(2+)spiking may be mediated by a redox sensitive mechanism affecting the sensitivity of Ca(2+)release from internal stores is proposed. At first mitosis, a small proportion of zygotes show low amplitude calcium spikes prior to pronuclear envelope breakdown (PNEBD), whereas all zygotes spiked at this time in the presence of high extracellular Ca(2+)and dithiothreitol. Nucleated zygotic fragments also spiked before PNEBD whereas anucleated ones rarely did. Exit from G2 was required for this spiking to be observed in nucleated zygotes or fragments. Arrest in M-phase resulted in the appearance of a prolonged series of small amplitude spikes. It is concluded that the spiking at mitosis is cell cycle regulated and may differ qualitatively in its control from that at fertilization.

Animals↗
PubMed2000

Storm flow export of metolachlor from a coastal plain watershed.

During an 18-month (1994-1995) survey of the surface water in an Atlantic Coastal Plain watershed, metolachlor was most frequently detected during storm flow events. Therefore, a sampling procedure, focused on storm flow, was implemented in June of 1996. During 1996, three tropical cyclones made landfall within 150 km of the watershed. These storms, as well as several summer thunderstorms, produced six distinct storm flow events within the watershed. Metolachlor was detected leaving the watershed during each event. In early September, Hurricane Fran produced the largest storm flow event and accounted for the majority of the metolachlor exports. During the storm event triggered by Hurricane Fran, the highest daily average flow (7.5 m2 s-1) and highest concentration (5.1 micrograms L-1) ever measured at the watershed outlet were recorded. Storm flow exports leaving the watershed represented 0.1 g ha-1 or about 0.04% of active ingredient applied.

Acetamides↗
PubMed1999

Cognitive modularity and genetic disorders.

This study challenges the use of adult neuropsychological models for explaining developmental disorders of genetic origin. When uneven cognitive profiles are found in childhood or adulthood, it is assumed that such phenotypic outcomes characterize infant starting states, and it has been claimed that modules subserving these abilities start out either intact or impaired. Findings from two experiments with infants with Williams syndrome (a phenotype selected to bolster innate modularity claims) indicate a within-syndrome double dissociation: For numerosity judgments, they do well in infancy but poorly in adulthood, whereas for language, they perform poorly in infancy but well in adulthood. The theoretical and clinical implications of these results could lead to a shift in focus for studies of genetic disorders.

Adult↗
PubMed1999

Genetically-targeted and conditionally-regulated ablation of astroglial cells in the central, enteric and peripheral nervous systems in adult transgenic mice.

Ablation of tissue regions, specific genes, or specific cell types represent important means of studying function in the nervous system. Here we summarize recent experience using a strategy for the genetically-targeted and conditionally regulated ablation of astroglial cells in different parts of the nervous system. The strategy is based on the targeted expression of herpes simplex virus thymidine kinase to astroglial cells using the glial fibrillary acid protein promoter in transgenic mice, combined with treatment with the antiviral agent ganciclovir. Under different experimental conditions we find that transgene-expressing astroglial cells can be selectively ablated by ganciclovir in the enteric nervous system, or in the injured forebrain or sciatic nerve, providing models in which to study the functions of these cells.

Animals↗
PubMed1999

A role for Rho-like GTPases in the polarisation of mouse eight-cell blastomeres.

Polarisation of cells during mouse preimplantation development first occurs within blastomeres at the eight-cell stage, as part of a process called compaction. Cell-cell contact mediated by the cell adhesion molecule uvomorulin (E-cadherin) and the activity of the microfilament cytoskeleton are important in the development of compaction, which is crucial for establishment of trophoblast and pluriblast (inner cell mass) lineages and for subsequent development. Members of the Rho family of p21 GTPases have been shown to regulate the organisation of the actin cytoskeleton and adhesion in other cell types. The potential role of these proteins in compaction was investigated. Inhibition of Rho with Clostridium botulinum C3-transferase disturbed intercellular flattening at compaction and prevented cytocortical microfilament polarisation of eight-cell blastomeres, in contrast to cytochalasin D which inhibited only adhesion. Microinjection of a constitutively activated recombinant Rho protein into four-cell blastomeres induced cortical microfilament disruption and apical displacement of nuclei associated with polarised clustering of microtubules. Interblastomere adhesion was reduced and E-cadherin was aberrently clustered at remaining cell-cell contacts. Similarly, activated Cdc42 protein induced nuclear displacement with additional cytoplasmic actin bundle formation between nucleus and cell-cell contacts. The effects produced by both of the activated GTPase proteins are indicative of prematurely induced but aberrently organised polarity. These results suggest that Rho family GTPases are involved in the polarisation of early mouse blastomeres.

ADP Ribose Transferases↗
PubMed1999

Practice patterns and clinical guidelines for posttreatment follow-up of head and neck cancers: a comparison of 2 professional societies.

OBJECTIVES: To determine and compare the current follow-up practice patterns of members of 2 professional societies of head and neck surgeons, and to compare these with the societies' published clinical practice guidelines. DESIGN: A survey was mailed to the 640 members of the American Society for Head and Neck Surgery (ASHNS); results were compared with those of a similar survey of the 824 members of the Society of Head and Neck Surgery (SHNS) and with the clinical practice guidelines of the consensus committee of both societies. MAIN OUTCOME MEASURES: Data were collected regarding the frequency of follow-up visits after potentially curative resection of head and neck epidermoid carcinoma and the types of diagnostic studies performed at each visit. RESULTS: A total of 318 ASHNS members responded to 1 of the mailings (49.7%), of which 280 responses (43.8%) were evaluable. Most surgeons relied on directed history, physical examination, and routine chest radiograph at varying intervals for detection of recurrences and second primary tumors. Other tests were used sporadically. For frequency of follow-up testing, the percentage of surgeons who followed the published guidelines varied from 97% in postoperative year 1 to 62% in postoperative year 5. A mean of 24% of surgeons varied from the guidelines in their use of chest radiographs, and 45% varied in their use of liver function tests. The ASHNS members used significantly more office visits than the SHNS members during the first 2 postoperative years. CONCLUSIONS: The strategies used by members of the ASHNS and the SHNS for posttreatment surveillance after potentially curative resection of malignant neoplasms of the head and neck were generally similar but showed some important differences. Most surgeons used directed history and physical examination at regular intervals, and annual chest radiographs. The follow-up practices of most members of these societies, which have recently merged, fall within the recommendations of the Clinical Guidelines Task Force.

Adult↗
PubMed1999

The activity of the H+-monocarboxylate cotransporter during pre-implantation development in the mouse.

We have reported previously that cytosolic pH (pHi) in the mouse 2-cell conceptus is controlled by a H+-monocarboxylate cotransporter (MCT) that is sensitive to cinnamates and p-chloromercuriphenylsulfonate. In the present study we have used measurement of pHi with BCECF to characterize the changes in MCT activity during pre-implantation development. We found that the resting pHi in bicarbonate-free conditions increased significantly from the unfertilized oocyte to the 2-cell stage, but thereafter remained constant. There was no evidence for changes in MCT activity during the cell cycle, but MCT activity was found to increase during development. Using RT-PCR we demonstrated that mRNA encoding MCT isoforms 1, 2 and 3 is present throughout pre-implantation development. The inhibitor of MCT1, p-chloromercuribenzoic acid, completely abolished the effect of extracellular l-lactate on pHi suggesting that MCT1, and not MCT2, plays a functional role in pHi regulation in mouse conceptuses, while the role of MCT3 remains unclear. We further found that removal of glucose from the culture medium, which has previously been shown to stimulate pyruvate uptake by blastocysts, had no effect on the activity of the MCT. These findings suggest that the changes in pyruvate uptake that have been observed following compaction are not due to changes in the activity of the MCT. These findings indicate the presence of MCTs during early embryonic development.

4-Chloromercuribenzenesulfonate↗
PubMed1999

Telemedical evaluation of ocular adnexa and anterior segment.

PURPOSE: To report the accuracy of telemedical slit-lamp evaluation in examination of ocular adnexa and anterior segment. METHODS: By means of contingency tables, slit-lamp findings by live examination and by real-time telemedicine were compared in 50 eyes of 25 patients. RESULTS: Sensitivity percentages (proportion with findings correctly identified by telemedicine)/specificity percentages (proportion without the finding that was correctly identified by telemedicine) were 100/64 for eyelid mass, 100/85 for conjunctival pigment, 100/100 for posterior synechiae, 80/0 for blepharitis, 83/93 for iridotomy, 70/93 for pinguecula, 75/93 for iris lesions, 56/98 for corneal scar, 0/100 for chamber inflammation, 57/93 for nuclear cataract, and 37/100 for intraocular lens presence. CONCLUSIONS: By means of monocular slit-lamp telemedical evaluation, clinical findings with high contrast cues for color and depth have the highest sensitivity and specificity.

Anterior Eye Segment↗
PubMed1999

Vascular lesions of the paranasal sinuses and nasal cavity.

The vascular supply to the face and paranasal sinuses is predominantly derived from branches of the external carotid artery. An extensive collateral arterial network exists between branches of the external carotid artery and the internal carotid artery that is important in the assessment of head and neck vascular disease. We illustrate the normal vascular anatomy and correlate cross-sectional and angiographic images of head and neck vascular disease, with a focus on lesions affecting the paranasal sinuses and nasal cavity.

Angiography↗
PubMed1999

Leukocyte infiltration, neuronal degeneration, and neurite outgrowth after ablation of scar-forming, reactive astrocytes in adult transgenic mice.

Reactive astrocytes adjacent to a forebrain stab injury were selectively ablated in adult mice expressing HSV-TK from the Gfap promoter by treatment with ganciclovir. Injured tissue that was depleted of GFAP-positive astrocytes exhibited (1) a prolonged 25-fold increase in infiltration of CD45-positive leukocytes, including ultrastructurally identified monocytes, macrophages, neutrophils, and lymphocytes, (2) failure of blood-brain barrier (BBB) repair, (3) substantial neuronal degeneration that could be attenuated by chronic glutamate receptor blockade, and (4) a pronounced increase in local neurite outgrowth. These findings show that genetic targeting can be used to ablate scar-forming astrocytes and demonstrate roles for astrocytes in regulating leukocyte trafficking, repairing the BBB, protecting neurons, and restricting nerve fiber growth after injury in the adult central nervous system.

Animals↗
PubMed1999

Cortical plasticity in normal and abnormal cognitive development: evidence and working hypotheses.

In this paper I review evidence and viewpoints on developmental plasticity in the cerebral cortex. Although there is some degree of plasticity in the cortex during early postnatal life in the human infant, this plasticity is constrained by various factors. Three working hypotheses about postnatal cortical specialization of function are advanced, and some specific predictions about the limits and extent of plasticity are assessed through both empirical evidence from infants and simulations on simple cortical network models.

Aging↗
PubMed1999

Ontogenetic constraints on neural and behavioral plasticity: evidence from imprinting and face processing.

This paper addresses the extent and limits on brain plasticity during development through the detailed study of imprinting in the domestic chick and the development of face processing in human infants. In both of these systems, evidence for constraints on plasticity is reviewed. The first source of constraint comes from the basic architecture of learning mechanisms that support plasticity. With regard to the chick, a specific "Hebbian" model based on the known neural circuitry of the region of the brain involved is presented and discussed. In human infants, a more abstract model inspired by cortical circuitry is mentioned. The second source of constraint comes from biases on the nature of the stimuli selected for attention by the young organism. Both in the chick and the human there is evidence for a subcortical brain system which orients their attention toward conspecifics, and particularly to their faces. It is argued that these systems tutor, or bias the input to, the more plastic learning systems.

Adaptation, Biological↗