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Biomedical subjects

R Kardon

Publications and source records attributed to R Kardon.

11 recordsLinked to original sources

MUC1/episialin: a critical barrier in the female reproductive tract.

The female reproductive tract must resist microbial infections as well as support embryonic development, implantation and placentation. Reproductive tract mucins, in general, and Muc1/episialin, in particular, play key roles in implantation related events and in protection from microbial infection. High levels of mucin expression in the lower reproductive tract presumably affords protection against infection while down-regulation of uterine mucins has been suggested to provide access to the uterine surface. The present studies demonstrate that mucins, particularly Muc1, are effective barriers to embryo attachment. Furthermore, a strain of female Muc1 null mice in normal housing displays chronic infection and inflammation of the lower reproductive tract and markedly reduced fertility rates. This phenotype is not observed when Muc1 nulls are housed in a pathogen-free environment indicating that this phenotype results from chronic microbial exposure. Only normal endogenous flora were isolated from the reproductive tracts of affected Muc1 null mice, suggesting that these bacterial species become opportunistic with loss of the mucin barrier. Staphylococcal adherence to lower reproductive tract epithelia was found to be mediated by cell surface mucin carbohydrates. Collectively, these studies demonstrate a critical barrier role for Muc1 in various aspects of female reproductive tract physiology.

Animals↗

Bacterial conjunctivitis in Muc1 null mice.

PURPOSE: In contrast to wild-type mice, genetically engineered Mucin1 (Muc1) null animals display a marked propensity for development of blepharitis and conjunctivitis. Molecular approaches confirmed the presence of Muc1 mRNA and protein in the conjunctival tissue of wild-type mice and identified the bacterial species in Muc1 null symptomatic mice. METHODS: Muc1 null animals housed in a conventional facility were examined for visually apparent inflammation of the eye and surrounding tissue. Blood taken from overtly affected animals was assayed for antibodies to common murine viral agents. Swabs of infected eyes and whole eye preparations were used to detect and speciate bacterial pathogens. Frozen sections of whole eye, lid margin, and Harderian gland were immunostained with antibodies to Muc1 and cytokeratin 14, both epithelial cell markers. Northern blot analysis and reverse transcription-polymerase chain reaction (RT-PCR) were performed on RNA isolated from conjunctiva and Harderian gland of wild-type mice to compare relative levels of transcript. RESULTS: Student's unpaired t-test performed on the eye inflammation frequency of Muc1 null mice confirmed a statistical significance (P < 0.01) when compared to wild-type background animals housed in the same room. Analysis of blood samples from affected Muc1 null animals detected no common murine viral pathogens. Bacterial analysis of conjunctival swabs and whole eye preparations demonstrated the presence of coagulase-negative Staphylococcus, Streptococcus type alpha, and Corynebacterium group G2. Muc1 antibody staining of wild-type sections revealed the presence of Muc1 on conjunctival goblet and non-goblet cells and on the epithelium of the Harderian gland. Serial sections stained with cytokeratin 14 antibody confirmed the epithelial nature of cells expressing the Muc1 protein. RNA from conjunctiva and Harderian gland subjected to RT-PCR and northern blot analysis showed an abundance of Muc1 transcript in these tissues. CONCLUSIONS: Muc1 mRNA and protein are present in murine conjunctival and Harderian gland epithelia. Animals lacking Muc1 mRNA and protein are predisposed to developing eye inflammation when compared to wild-type animals with an intact Muc1 gene. Muc1 appears to play a critical protective role at the ocular surface, presumably by acting as a barrier to infection by certain bacterial strains.

Animals↗

Late-onset Leber's hereditary optic neuropathy.

Progressive, sequential visual loss in the left and then right eye was reported in a 73-year-old male over three months. The presence of a family history of visual loss and the lack of other findings in association with bilateral cecocentral scotomata led to a diagnosis of new onset Leber's hereditary optic neuropathy, confirmed by the presence of a mutation at the 11,778 position. This case illustrates that Leber's hereditary optic neuropathy may manifest late in life.

Aged↗

Cloning and structural organization of the gene encoding the murine nuclear receptor transcription factor, NURR1.

NURR1 is an immediate early gene product and a member of the nuclear receptor superfamily of transcription factors. Using the NURR1 cDNA as a probe, we isolated the genomic DNA encoding NURR1 from a mouse 129SvEv genomic library. The NURR1 gene is approximately 6.2 kb long and is organized into 7 exons separated by 6 introns. Structural analysis of the NURR1 reveals that this gene shares a similar structure with that of the nuclear receptor NUR77/NGF1-B. As in NUR77, the promoter region of NURR1 lacks an identifiable TATA box, but is GC-rich. The proximal promoter region also contains an ATF/CREB consensus binding site that may participate in cAMP-mediated induction of this immediate early gene product. Isolation and structural characterization of the NURR1 gene provides information for further developmental and transcriptional regulation studies of this gene.

Activating Transcription Factor 1↗

Idiopathic intracranial hypertension. Lack of histologic evidence for cerebral edema.

OBJECTIVE: To study brain histologic features in two cases of idiopathic intracranial hypertension (pseudotumor cerebri) at autopsy. DESIGN: Formaldehyde solution-fixed sections of cerebral white matter in two cases and structures of the sensory visual system in one case were analyzed. SETTING: University medical center. PATIENTS: Two patients with idiopathic intracranial hypertension who died unexpectedly. MAIN OUTCOME MEASURE: Histologic study of cerebral white matter in the two patients. RESULTS: We did not find histologic evidence of any type of cerebral edema in our patients. Review of a portion of the material from a previous report is also consistent with this conclusion. CONCLUSION: If patients with idiopathic intracranial hypertension have histologically apparent cerebral edema, it is not a consistent finding.

Adult↗

Pupillary light reflex.

A wealth of new information has recently come to light concerning the pupillary response to various types of visual input. Much of this information is recent, and has either been published in the last year, is in press, or has just been reported at meetings. This new information is important because it is resulting in reexamination of the pupillary input pathways and the clinical role for using pupillary movements to understand the physiology and pathology of the visual system. This review will focus on this new information and its clinical implication. The review is organized in the following sections: 1) the pupillary response to full-field, global light stimuli; 2) "pupil perimetry" or the pupillary response to focal light stimuli; 3) the pupillary response to isoluminant stimuli, eg, color spatial frequency, motion; 4) receptive field organization in the pupillary light reflex pathway.

Humans↗

Neuro-ophthalmic complications of intracranial catheters.

We report four patients who sustained direct injury to the brain after insertion of intraventricular shunts and pressure monitoring lines, which resulted in permanent neuro-ophthalmic deficits. These included hemianopsia from an optic tract lesion, esotropia and residual bilateral facial paresis from dorsal pontine injury, unilateral blindness from damage to the optic nerve, and dorsal midbrain syndrome from catheter compression in the region of the posterior commissure. Although presumably rare, such injuries should be considered in diagnosing patients with neuro-ophthalmic complaints after insertion of such devices.

Adult↗

Dysfunctional grieving.

Dysfunctional grieving represents a failure to follow the predictable course of normal grieving to resolution (Lindemann, 1944). When the process deviates from the norm, the individual becomes overwhelmed and resorts to maladaptive coping. The process implies movement toward assimilation to or accommodation of the loss, resulting in progression toward social, psychological, and medical morbidity. Nurses will better assess the needs of the client with adequate information about the client's recent losses and perception of those losses. Such an assessment, in conjunction with an understanding of the signs, symptoms, and predisposing factors of complicated bereavement, will enable the nurse to develop a plan of effective intervention. Both case examples illustrate unresolved grief. In Case Example 1, the patient denied the importance of the relationship, which became masked with displaced anger and therefore delayed the grieving process. In Case Example 2, the patient's attempts at grieving over the loss of her son were complicated by her long-standing struggle with her husband's infidelity at the time of her pregnancy. The revelation of secondary loss is common in dysfunctional grieving. Resolution of grief encompasses not only accommodation to object loss, but also change in the pathological behaviors incorporated into the patient's self-image as a result of the loss (Lazare, 1979). The maladaptive operations employed by these patients to preserve self-image were discarded as the grief resolved. The focus of therapy included the loss of those behaviors as they were relinquished to prevent the patient from experiencing further anxiety and sense of loss (Zisook, 1987).(ABSTRACT TRUNCATED AT 250 WORDS)

Adaptation, Psychological↗

Early magnetic resonance imaging in acute traumatic internuclear ophthalmoplegia.

Adduction deficiency following acute head trauma may result not only from orbital damage but also from internuclear ophthalmoplegia, and in most instances this resolves over weeks to months. To date, noninvasive imaging studies during the acute phase following injury have not been definitive in localizing the pathology. Three cases of adduction deficiency following head trauma that were caused by internuclear ophthalmoplegia are reported. A lesion in the brain stem was found in all three cases by magnetic resonance imaging in the subacute post-traumatic period. These lesions were not visible on routine x-ray computed tomography obtained at the time of injury.

Adolescent↗

Two neuro-ophthalmic episodes separated in time and space.

A-46-year-old woman with a prior history of a spontaneously resolving right central retinal artery occlusion presented with an acute right third order Horner's syndrome and vague ocular pain. Magnetic resonance angiography demonstrated a right internal carotid artery dissection. The dissection improved on anticoagulation therapy. Marfans syndrome or Ehlers-Danlos syndrome was suspected but ruled out by clinical criteria and skin biopsy respectively.

Anticoagulants↗

Mucin expression and function in the female reproductive tract.

Reproductive tract epithelia are characterized by the presence of a thick, apical glycocalyx. This glycoprotein coat is drastically reduced in the uterus of many species during the time of embryo implantation. Recent studies indicate that mucin glycoproteins constitute a large proportion of the apical glycocalyx. One of these mucins, Muc-1, has particularly important functions at the luminal surface of the uterus and other female reproductive tract tissues. Muc-1 appears to play a dominant role in maintaining a functionally non-receptive uterine surface with regard to blastocyst attachment. Conversion to a receptive uterine state is brought about by the concerted actions of ovarian steroid hormones that in several species also strongly modulate Muc-1 protein and mRNA expression. Muc-1 also appears to serve a general function in protecting reproductive tract mucosa since Muc-1 null mice are particularly prone to bacterial infection. Collectively, these studies indicate that mucins, including Muc-1, play important barrier roles in reproductive processes and protection from bacterial pathogenesis in the female reproductive tract.

Animals↗