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Biomedical subjects

K M Miller

Publications and source records attributed to K M Miller.

At least 19 recordsLinked to original sources
PubMed2006

Major histocompatibility complex and kin discrimination in Atlantic salmon and brook trout.

Many species of salmonids can discriminate kin from unrelated conspecifics using olfactory cues. In this study, we determined the role of the major histocompatibility complex (MHC) in kin discrimination by juvenile Atlantic salmon (Salmo salar) and brook trout (Salvelinus fontinalis). Genetic variation at the highly polymorphic exon coding for peptide-binding region of an MHC class II gene was studied using polymerase chain reaction and denaturing gradient gel electrophoresis. Experiments compared discrimination ability based on MHC haplotypes both within and among kin and non-kin groups. Juveniles chose kin sharing both alleles over kin sharing no alleles. Juveniles also preferred non-kin sharing both alleles to non-kin sharing no alleles. These data suggest that the MHC class II gene influence kin discrimination in juvenile Atlantic salmon and brook trout. The influence of additional genes was also apparent in trials where juveniles were able to recognize kin sharing no alleles over non-kin sharing no alleles. However, the inability of juveniles to discriminate between kin sharing no alleles and non-kin sharing either one or both alleles indicates that MHC is as potent as the rest of the genome in producing distinguishable odours.

Alleles↗
PubMed2005

Genetic variation within and among domesticated Atlantic salmon broodstocks in British Columbia, Canada.

Atlantic salmon have been reared in the British Columbia, Canada aquaculture industry since the early 1980s. No breeding programmes spanned the entire production period and pedigree records were not kept for broodstocks prior to or since importation. Of the three recognized industry strains, two are of European ancestry ('Mowi' from Norway and 'McConnell' from Scotland) and one is of North American heritage ('Cascade' from Gaspe, Quebec). We evaluated the amount and distribution of genetic variation within industry broodstocks by surveying microsatellite variation at 11 loci in 20 broodstock groups sampled from major production facilities. Allelic richness averaged 10.9 (range 5.8-13.8), compared with a value of 20.3 obtained for a North American wild population. Pairwise genetic distances (D(S)) between samples within strains were generally less than those between strains, with samples attributed to the same strain clustering together in a neighbour-joining dendrogram. Nevertheless, average distances between samples within the European strains were high (0.41 for Mowi; 0.71 for McConnell) but lower (0.06) for the Cascade strain. The reduced intra-sample and increased intra-strain genetic variation observed for the BC domesticated samples compared with wild populations was similar to observations for European domesticated Atlantic salmon. Evidence of introgression of the Cascade strain into European broodstocks was provided by the presence of large Ssa202 alleles (confined to North America in wild populations) in some Mowi and McConnell samples. Introgression likely also contributed to the decreased intercontinental genetic distance for the domesticated samples of this study compared with that observed for wild populations.

Alleles↗
PubMed2004

Characterisation of matrix metalloproteinases and the effects of a broad-spectrum inhibitor (BB-1101) in peripheral nerve regeneration.

The effect of treatment with a broad-spectrum inhibitor (BB1101) of the matrix metalloproteinases (MMPs) on nerve regeneration and functional recovery after nerve crush was examined. Drug treatment had no effect on latency but from 63 days the compound muscle action potential was significantly increased and was no different to that in the sham-operated controls at 72 days. Levels of MMP mRNA expression, and the localisation and activity of MMP proteins, were examined in rats for a 2 month period following a nerve crush injury, and compared with sham-operated controls. The mRNA of all the MMPs studied was up-regulated by 5-10 days after nerve crush, and they remained up-regulated for 40-63 days, except for MMP-9 which was down-regulated by 10 days. MMP immunoreactivity was localised to Schwann cells, macrophages and endothelial cells, and with the exception of membrane type 1-MMP (MT1-MMP), it was more intense after nerve crush compared with sham-operated controls. Regenerating axons showed immunoreactivity for MMP-2 and MMP-3. In situ zymography confirmed that the activity of MMPs in the nerve was increased following crush but that the activity was greatly reduced in rats treated with BB-1101. Thus despite the inhibition of MMPs by BB-1101, the drug did not appear to essentially affect nerve degeneration or regeneration following nerve crush but that it could be beneficial in promoting the more effective reinnervation of muscles possibly by actions at the level of the muscles.

Action Potentials↗
PubMed2002

Comparison of matrix metalloproteinase expression during Wallerian degeneration in the central and peripheral nervous systems.

The matrix metalloproteinases (MMPs) are a large family of zinc-dependent enzymes which are able to degrade the protein components of the extracellular matrix. They can be placed into subgroups based on structural similarities and substrate specificity. Aberrant expression of these destructive enzymes has been implicated in the pathogenesis of immune-mediated neuroinflammatory disorders. In this study we investigate the involvement of MMPs, from each subgroup, in Wallerian degeneration in both the central and peripheral nervous systems. Wallerian degeneration describes the process initiated by transection of a nerve fibre and entails the degradation and removal of the axon and myelin from the distal stump. A similar degenerative process occurs as the final shared pathway contributing to most common neuropathies. MMP expression and localisation in the peripheral nervous system are compared with events in the CNS during Wallerian degeneration. Within 3 days after axotomy in the peripheral nervous system, MMP-9, MMP-7 and MMP-12 are elevated. These MMPs are produced by Schwann cells, endothelial cells and macrophages. The temporospatial expression of activated MMP-9 correlates with breakdown of the blood-nerve barrier. In the CNS, 1 week after optic nerve crush, four MMPs are induced and primarily localised to astrocytes, not microglia or oligodendrocytes. In the degenerating optic nerve, examined at later time points (4, 8, 12 and 18 weeks), MMP expression was down-regulated. The absence of MMPs in oligodendrocytes and mononuclear phagocytes during Wallerian degeneration may contribute to the slower removal of myelin debris observed in the CNS. The low level of the inactive pro-form of MMP-9 in the degenerating optic nerve may explain why the blood-brain barrier remains intact, while the blood-nerve barrier is rapidly broken down. We conclude that the difference in the level of expression, activation state and cellular distribution of MMPs may contribute to the different sequence of events observed during Wallerian degeneration in the peripheral compared to the CNS.

Animals↗
PubMed2001

Ophthalmology inpatient consultation.

OBJECTIVE: To profile inpatients and eye problems evaluated and managed by the Ophthalmology Consultation Service of a large university teaching hospital. DESIGN: A hospital-based retrospective, cross-sectional study. PARTICIPANTS: One thousand four hundred seventy-two patients admitted to the University of California Los Angeles Medical Center. METHODS: We reviewed the inpatient medical records, discharge summaries, and Ophthalmology Consultation Service notes of every patient evaluated by the Service from July 1990 through January 1997. MAIN OUTCOME MEASURES: We recorded demographic information, hospitalization information, and eye examination information, including reason for consultation, type of consultation (screening examination, new eye problem, or preexisting eye problem), as well as primary and secondary ophthalmologic diagnoses. RESULTS: Internal medicine services requested 39.7% of consultations, surgery services 20.9%, and trauma services 13.5%. There were 92 different reasons why consultations were requested. The most common reason was decreased vision. Eye problems that developed either on the day of admission or some time during hospitalization accounted for 39.6% of consultations, preexisting eye problems accounted for 31.6%, and screening examinations for the remaining 28.7%. We recorded 166 unique primary ophthalmologic diagnoses and 130 unique secondary ophthalmologic diagnoses. The top five common primary ophthalmologic diagnoses were refractive error (88 patients), fungal endophthalmitis ruled out (80 patients), conjunctivitis (56 patients), diabetic retinopathy (52 patients), and corneal abrasion (52 patients). Refractive error was the most common secondary ophthalmologic diagnosis (201 patients). Inpatient diagnostic or surgical procedures were performed 7911 times. There were 947 unique primary and 1391 unique secondary hospital discharge diagnoses. The most common primary discharge diagnosis, human immunodeficiency virus infection, accounted for only 1.6% of all hospitalizations, indicating a considerable diversity of systemic disease in the study population. CONCLUSIONS: This study profiled the typical patients and eye problems an ophthalmologist may expect to encounter when inpatient consultation is requested. The information may be useful for the planning and management of consultation services in residency training programs.

Adolescent↗
PubMed2001

Geographic heterogeneity in natural selection on an MHC locus in sockeye salmon.

Balancing selection maintains high levels of polymorphism and heterozygosity in genes of the MHC (major histocompatibility complex) of vertebrate organisms, and promotes long evolutionary persistence of individual alleles and strongly differentiated allelic lineages. In this study, genetic variation at the MHC class II DAB-beta1 locus was examined in 31 populations of sockeye salmon (Oncorhynchus nerka) inhabiting the Fraser River drainage of British Columbia, Canada. Twenty-five percent of variation at the locus was partitioned among sockeye populations, as compared with 5% at neutral genetic markers. Geographic heterogeneity of balancing selection was detected among four regions in the Fraser River drainage and among lake systems within regions. High levels of beta1 allelic diversity and heterozygosity, as well as distributions of alleles and allelic lineages that were more even than expected for a neutral locus, indicated the presence of balancing selection in populations throughout much of the interior Fraser drainage. However, proximate populations in the upper Fraser region, and four of six populations from the lower Fraser drainage, exhibited much lower levels of genetic diversity and had beta1 allele frequency distributions in conformance with those expected for a neutral locus, or a locus under directional selection. Pair-wise FST values for beta1 averaged 0.19 and tended to exceed the corresponding values estimated for neutral loci at all levels of population structure, although they were lower among populations experiencing balancing selection than among other populations. The apparent heterogeneity in selection resulted in strong genetic differentiation between geographically proximate populations with and without detectable levels of balancing selection, in stark contrast to observations at neutral loci. The strong partitioning and complex structure of beta1 diversity within and among sockeye populations on a small geographic scale illustrates the value of incorporating adaptive variation into conservation planning for the species.

Alleles↗
PubMed2001

Motor deficits in fibroblast growth factor receptor-3 null mutant mice.

Fibroblast growth factor receptor-3 (FGFR-3) regulates aspects of bone development. Mutations in the FGFR-3 gene (Fgfr3) in humans and mice produce vertebral abnormalities and bone deformities. The present study evaluated the behavioural concomitants of the Fgfr3-/- mutation. Fgfr3-/- null mutant mice displayed severe impairments of motor abilities as detected on the rotarod, wire hang and open field tests. Absence of prepulse inhibition of acoustic startle was seen at prepulse levels from 74 to 86 dB. The motor deficits appear to be a direct and predicted consequence of the skeletal kyphosis, scoliosis and long bone overgrowth previously reported in Fgfr3 null mutant mice. The behavioural phenotype displayed by these mutant mice complements their anatomical, physiological and biochemical phenotypes, to complete the characterization of the functional outcome of a single gene mutation. Simple, robust behavioural symptoms, such as poor rotorod performance in Fgfr3 knockout mice, can provide useful surrogate markers to evaluate pharmacological treatments and gene therapies for human genetic diseases.

Animals↗
PubMed2001

Cataract surgery after retinal surgery.

Many patients require surgery for cataract after retinal surgery. When evaluating patients preoperatively, the surgeon should pay careful attention to the assessment of visual function and potential acuity, and to the slit lamp examination of the lens, posterior capsule, anterior cortical vitreous, and zonules. The surgeon's technique must account for increased nuclear sclerosis, intraoperative miosis, a characteristically longer axial length, and fluctuations in anterior chamber depth from movement of the iris-lens diaphragm. Posterior capsule plaques are not unusual. Posterior capsule opacification is the most frequent late complication. Visual outcomes are usually good except when limited by pre-existing macular pathology. Vision-threatening complications of cataract surgery are unusual.

Cataract↗
PubMed2000

Suppression of apoptosis induced by growth factor withdrawal by an oncogenic form of c-Cbl.

The v-Cbl oncogene induces myeloid and B-cell leukemia; however, the mechanism by which transformation occurs is not understood. An oncogenic form of c-Cbl (Cbl-DeltaY371) was expressed in the interleukin-3 (IL-3)-dependent cell line 32Dcl3 to determine whether it was able to induce growth factor-independent proliferation. We were unable to isolate clones of transfected 32Dcl3 cells expressing Cbl-DeltaY371 that proliferated in the absence of IL-3. In contrast, 32Dcl3/Cbl-DeltaY371 cells did not undergo apoptosis like parental 32Dcl3 cells when cultured in the absence of IL-3. Both 32Dcl3 and 32D/CblDeltaY371 cells arrested in G(1) when cultured in the absence of IL-3. Approximately 18% of the 32Dcl3 cells cultured in the absence of IL-3 for 24 h were present in a sub-G(1) fraction, while only 4% of the 32D/Cbl-DeltaY371 and 2% of the 32D/Bcl-2 cells were found in a sub-G(1) fraction. There was no difference in the pattern of tyrosine-phosphorylated proteins observed following stimulation of either cell type with IL-3. The phosphorylation of JAK2, STAT5, and endogenous c-Cbl was identical in both cell types. No differences were detected in the activation of Akt, ERK1, or ERK2 in unstimulated or IL-3-stimulated 32D/Cbl-DeltaY371 cells compared with parental 32Dcl3 cells. Likewise, there was no difference in the pattern of phosphorylation of JAK2, STAT5, ERK1, ERK2, or Akt when 32Dcl3 and 32D/CblDY371 cells were withdrawn from medium containing IL-3. The protein levels of various Bcl-2 family members were examined in cells grown in the absence or presence of IL-3. We observed a consistent increased amount of Bcl-2 protein in five different clones of 32D/Cbl-DeltaY317 cells. These data suggest that the Cbl-DeltaY371 mutant may suppress apoptosis by a mechanism that involves the overexpression of Bcl-2. Consistent with this result, activation of caspase-3 was suppressed in 32D/Cbl-DeltaY371 cells cultured in the absence of IL-3 compared with 32Dcl3 cells cultured under the same conditions.

3T3 Cells↗
PubMed2000

Matrix metalloproteinase (MMP)-8 and MMP-9 in cerebrospinal fluid during bacterial meningitis: association with blood-brain barrier damage and neurological sequelae.

To evaluate the spectrum and regulation of matrix metalloproteinases (MMPs) in bacterial meningitis (BM), concentrations of MMP-2, MMP-3, MMP-8, and MMP-9 and endogenous inhibitors of metalloproteinases (TIMP-1 and TIMP-2) were measured in the cerebrospinal fluid (CSF) of 27 children with BM. MMP-8 and MMP-9 were detected in 91% and 97%, respectively, of CSF specimens from patients but were not detected in control patients. CSF levels of MMP-9 were higher (P<.05) in 5 patients who developed hearing impairment or secondary epilepsy than in those who recovered without neurological deficits. Levels of MMP-9 correlated with concentrations of TIMP-1 (P<.001) and tumor necrosis factor-alpha (P=.03). Repeated lumbar punctures showed that levels of MMP-8 and MMP-9 were regulated independently and did not correlate with the CSF cell count. Therefore, MMPs may derive not only from granulocytes infiltrating the CSF space but also from parenchymal cells of the meninges and brain. High concentrations of MMP-9 are a risk factor for the development of postmeningitidal neurological sequelae.

Blood-Brain Barrier↗
PubMed2000

Increased expression of osteonectin/SPARC mRNA and protein in age-related human cataracts and spatial expression in the normal human lens.

PURPOSE: We have previously reported increased levels of Osteonectin/SPARC transcript in age-related cataractous compared to normal human lenses. The purpose of the present study was to evaluate the corresponding levels of osteonectin/SPARC protein in age-related cataractous relative to normal lenses and to evaluate the levels of osteonectin/SPARC transcript in specific types of age-related human cataracts. The spatial expression of osteonectin/SPARC was also evaluated in normal human lenses. METHODS: Specific types of age-related cataracts were collected and graded. Normal human lenses were microdissected into epithelia and fibers. Osteonectin/SPARC protein levels were monitored by Western immunoblotting, and transcript levels were evaluated by reverse transcriptase polymerase chain reaction (RT-PCR). Osteonectin/SPARC expression patterns were examined by RT-PCR and by immunostaining. RESULTS: Higher levels of osteonectin/SPARC protein were detected in age-related cataractous relative to normal human lenses. Increased levels of osteonectin/SPARC transcript were also detected in posterior-subcapsular and nuclear cataractous lenses relative to normal lenses. Osteonectin/SPARC transcripts were detected in the lens epithelium but not fibers. Osteonectin/SPARC protein levels were highest in the peripheral lens epithelium. CONCLUSIONS: Consistent with our previous studies on osteonectin/SPARC mRNA levels, osteonectin/SPARC protein levels were also elevated in cataractous compared to normal human lenses. Increased levels of osteonectin/SPARC mRNA were also found in nuclear and posterior-subcapsular cataracts relative to normal lenses. Osteonectin/SPARC expression is confined to the lens epithelium, and osteonectin/SPARC levels are highest in the peripheral lens epithelium.

Adolescent↗
PubMed2000

Phacoemulsification and lens implantation after scleral buckling surgery.

PURPOSE: To determine the intraoperative and postoperative complications and best-corrected visual acuity outcomes of eyes undergoing phacoemulsification and intraocular lens implantation after retinal detachment repair by the scleral buckling technique. METHODS: The charts of all patients who underwent phacoemulsification and intraocular lens implantation between July 1991 and May 1998 in two surgical practices were reviewed to identify eyes with a history of retinal detachment repaired by the scleral buckling technique. Eyes with a history of pars plana vitrectomy were excluded. Demographic and surgical data, preoperative and postoperative best-corrected visual acuity, and intraoperative and postoperative complications were recorded. RESULTS: We identified 34 eyes of 32 patients. The mean interval from retinal detachment repair to phacoemulsification was 12.4 years. The mean interval from phacoemulsification to final examination was 20 months. Risk factors for retinal detachment included isolated myopia (82%), myopia with lattice retinal degeneration (5.9%), and myopia with trauma (8.8%). One eye (2.9%) had no identifiable risk factors. Final best-corrected visual acuity of 20/40 or better was attained in 29 (85%) of 34 eyes and 20/20 or better in 18 (53%) of the eyes. Of the five eyes with the lowest best-corrected visual acuity, three had a macula-off retinal detachment; one had a posterior capsule opacity, epiretinal membrane, and corneal edema secondary to ocular ischemia; and one had advanced glaucoma. All five eyes still experienced an improvement in best-corrected visual acuity. With regard to complications, one eye had a posterior capsular tear with vitreous loss and another developed a postoperative retinal tear. Posterior capsule opacification requiring laser capsulotomy developed in 13 eyes (38%). No eye developed a retinal redetachment. CONCLUSION: Phacoemulsification and intraocular lens implantation can be performed safely after scleral buckling surgery and excellent best-corrected visual acuity results can be attained in most eyes. No modification of surgical technique is necessary. No retinal redetachment occurred in this series.

Adult↗
PubMed2000

Posterior dislocation of a plate-haptic silicone intraocular lens with large fixation holes.

We present a patient who had uneventful phacoemulsification with in-the- bag implantation of a silicone plate-haptic posterior chamber intraocula r lens (IOL) with 1.15 mm fixation holes. Six months after a neodymium: YAG laser capsulotomy, the IOL spontaneously dislocated posteriorly. A pars plana vitrectomy was performed, the IOL was explanted, and a 3-piece loop-haptic IOL was implanted in the ciliary sulcus. Eight weeks after surgery, best corrected visual acuity was 20/20.

Aged↗
PubMed2000

Outcomes of cataract surgery in monocular patients.

PURPOSE: To determine the best corrected visual acuity (BCVA) outcomes and surgical complications in a consecutive series of functionally monocular patients who had phacoemulsification and intraocular lens (IOL) implantation. SETTING: University-based referral practice, Los Angeles, California, USA. METHODS: The medical records of 93 monocular patients who had phacoemulsification and IOL implantation between December 1991 and February 1999 were reviewed. Patients were considered to be monocular if Snellen BCVA in their fellow eye (the eye not having surgery) was worse than 20/200. Recorded were demographic information, anesthesia method, additional surgery, IOL model, preoperative and postoperative BCVA, reason for poor vision in the unoperated eye, co-morbidities in the operated eye, intraoperative and postoperative complications, length of follow-up, and postoperative procedures. RESULTS: Mean patient age was 72 years and mean follow-up, 6 months. Thirteen patients (14%) were monocular from complications of surgery. Eighty patients (86%) were monocular because of medical eye conditions. Ocular co-morbidities were present in 75% of eyes having surgery. Preoperative median BCVA was 20/60. Median BCVA was 20/30 by the final scheduled follow-up examination and 20/25 by the final follow-up examination. Thirty-seven percent of eyes were correctable to 20/20 or better, and 67% were correctable to 20/40 or better. Two eyes lost BCVA by the final scheduled postoperative examination, and 3 eyes lost BCVA by the final follow-up examination. Final BCVA of worse than 20/40 was always related to preexisting macular or optic-nerve pathology. There were 16 intraoperative or early postoperative complications. The most common (3 eyes) was posterior capsule plaque that could not be removed by capsule polishing. Twenty eyes (22%) had subsequent surgical procedures, the most common being laser posterior capsulotomy. No patient who was monocular from surgical complications had similar problems with second-eye cataract surgery. CONCLUSIONS: Best corrected visual acuity, the standard measure of efficacy in cataract surgery, improved a median of 3 to 4 Snellen lines. The safety of the procedure, as evidenced by the small number of patients who lost BCVA or experienced surgical complications, was satisfactory. Functionally monocular patients are likely to have ocular co-morbidities, some of which may limit the final visual outcome of surgery.

Adult↗
PubMed2000

Visual complaints associated with the AcrySof acrylic intraocular lens(1).

PURPOSE: To describe the visual complaints of a series of patients implanted with the AcrySof(R) (Alcon Surgical) acrylic intraocular lens (IOL) that resolved with IOL exchange. SETTING: Jules Stein Eye Institute, Los Angeles, California, and John A. Moran Eye Center, Salt Lake City, Utah, USA. METHODS: This was a retrospective review of patients who had AcrySof IOL exchange from January 1997 to December 1998. RESULTS: Eight patients (9 eyes) with bothersome visual symptoms following AcrySof IOL implantation were identified. Problems included glare, halos around point light sources, and peripheral arcs of light, often worse at night. In each case, the IOL was well-centered in the capsular bag and there was no significant posterior capsule opacification. Six patients (7 eyes) had the MA30BA model with a 5.5 mm optic, and 2 patients (2 eyes) had the MA60BM model with a 6.0 mm optic. No extralenticular reasons for the patients' complaints could be identified. Exchanging the AcrySof IOLs with silicone or poly(methyl methacrylate) IOLs alleviated most symptoms. In 5 of 8 patients, dysphotopsias resolved completely. CONCLUSIONS: A small number of patients implanted with AcrySof IOLs have specific complaints of glare, halos, and peripheral arcs of light. Optical considerations that may help explain these symptoms include the high refractive index of the IOL material and the truncated design of the optic. Patients who are highly observant and those with large pupils may be particularly symptomatic. Intraocular lens exchange may be necessary in some cases.

Acrylates↗
PubMed2000

Digital overlay technique for documenting toric intraocular lens axis orientation.

PURPOSE: To describe a digital overlay technique for documenting toric intraocular lens (IOL) axis alignment. SETTING: Jules Stein Eye Institute and the Department of Ophthalmology, University of California at Los Angeles School of Medicine, Los Angeles, California, USA. METHODS: Digital overlay imaging was used to evaluate the alignment of Staar toric IOLs in 4 eyes of 3 patients who had regular corneal astigmatism at the time of cataract surgery. Lens axes were determined by computerized analysis of digitally scanned retroillumination photographs. A stock digital image of a Staar AA4203TF toric IOL was superimposed on corneal topography images to document IOL alignment with the steep corneal meridian. RESULTS: Digital overlay images demonstrated that 3 IOLs in the sample group were within 5 degrees and 1 was within 20 degrees of the intended axis at the time of the final postoperative examination. Slitlamp lens axis estimations were 3 to 18 degrees different from that determined by this technique. CONCLUSION: Digital overlay imaging of correctly oriented toric IOLs on computerized corneal topography maps represents an intuitive, accurate, and visually appealing method of documenting toric IOL axis alignment.

Aged↗