PubMed Health⌕ Search

Biomedical subjects

K D Miller

Publications and source records attributed to K D Miller.

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

The effect of the Halothane and Rendement Napole genes on carcass and meat quality characteristics of pigs.

The objective of this study was to determine the effects of the Halothane (N) and Rendement Napole (RN) genes on carcass and meat quality characteristics in pigs. Halothane and RN carrier (Nn/RN- rn+) Hampshire boars (n = 4) were mated to dams that were homozygous for the normal allele of both genes (NN/rn+ rn+) to produce progeny of four genotypes: 1, NN/rn+ rn+ (n = 31); 2, Nn/rn+ rn+ (n = 27); 3, NN/RN- rn+) (n = 30); and 4, Nn/RN- rn+ (n = 23). A DNA test was used to determine Halothane genotype, and longissimus glycolytic potential was used to predict the RN genotype. Pigs were reared under standard conditions to approximately 120 kg live weight and slaughtered at a commercial plant, and carcass characteristics and meat quality were evaluated. Halothane carriers (Nn/ _ _), in comparison to Halothane normal (NN/_ _) pigs, had shorter carcasses, lower longissimus ultimate pH, higher Minolta L* and b* values, and greater drip loss. Rendement Napole gene carriers (_ _/RN- rn+) had higher L* and b* values and drip and cooking loss and lower longissimus ultimate pH than homozygous recessive animals (_ _/rn+ rn+). There were Halothane x RN genotype interactions (P < 0.05) for subjective color, firmness, and marbling scores, and for shear force. Animals that were normal for both genes (NN/rn+ rn+) had the highest subjective scores for color (2.60, 1.88, 1.85, and 1.95, SE = 0.181, P < 0.05), firmness (2.53, 2.03, 2.10, and 1.89, SE = 0.182, P < 0 .05), and marbling (2.11, 1.44, 1.53, and 1.55, SE = 0.153, P < 0 .05) for genotypes 1, 2, 3, and 4, respectively, suggesting darker, firmer muscle with a higher level of marbling for this genotype. Shear force was highest for Nn/rn+ rn+ animals (3.83, 4.41, 3.79, and 3.70, respectively, SE = 0.172, P < 0.05). Gilts had less s.c. backfat thickness, greater longissimus muscle area, and lower subjective marbling scores than barrows. There was no effect (P > 0.05) of gender on other meat quality traits. This study illustrates the negative effects of the Halothane and RN genes on fresh pork quality and suggests that in combination the detrimental effects of the two genes are additive for ultimate pH, objective color, and water-holding capacity.

Alleles↗
PubMed2000

Frequency of the Rendement Napole RN- allele in a population of American Hampshire pigs.

A total of 204 purebred Hampshire pigs were obtained from 23 breeders. These animals were the progeny of 41 sires and 123 dams. A sample of purebred Yorkshire (n = 24) pigs were also used in the study. Animals were classified by glycolytic potential determined on a live-animal longissimus muscle biopsy sample. Hampshire pigs (n = 176) with glycolytic potential greater than 185 micromol/g (x = 238.8 micromol/g; SD = 29.54) were classified as heterozygous or homozygous for the dominant RN- allele (RN-rn+ or RN-RN-, respectively), whereas cohorts (n = 28) with glycolytic potential less than 185 micromol/g (x = 141.3 micromol/g; SD = 24.48) were considered as homozygous normal (rn+rn+). All Yorkshire pigs (n = 24) had a mean glycolytic potential level of 146.1 micromol/g (SD = 20.18) and were considered as homozygous normal (rn+rn+). The Hardy-Weinberg equilibrium yielded frequencies of .630 and .370 for the dominant RN- allele and normal rn+ alleles in the Hampshire population, respectively, and genotypic frequencies of .397 (RN-RN-), .466 (RN-rn+), and .137 (rn+rn+). Hampshires with glycolytic potential > or = 185 micromol/g had significantly lower longissimus muscle ultimate pH, intramuscular fat, subjective marbling scores, and percentage of protein (P < .001) and had greater longissimus muscle percentage of moisture (P < .001), drip loss (P < .01), and cooking loss (P < .001) than rn+rn+ Hampshires and Yorkshires. These data suggest the RN- allele exists at a high frequency within the American Hampshire breed. Higher glycolytic potential levels, which accompany the allele, may cause decreased meat quality.

Alleles↗
PubMed2000

Primary yolk sac tumor of the rectum.

Extragonadal germ cell tumors are well recognized in men but have rarely been reported in women. Reports have primarily focused on the pediatric population and have suggested a poor prognosis for extragonadal yolk sac tumors. A 23-year-old woman with a yolk sac tumor arising in the rectum is described. A review of the English-language literature (MEDLINE 1966-1998) regarding extragonadal germ cell tumors in females is provided. Treatment with four courses of cisplatin, etoposide, and bleomycin was followed by surgical resection of the involved area. No residual tumor was identified. She remains disease free 3.5 years later. Previous reports are limited by the small number of patients, focus on the pediatric population, and treatment before the availability of cisplatin. Extragonadal germ cell tumors in women are extremely rare but can be successfully treated with aggressive chemotherapy and surgery similar to testis cancer.

Adult↗
PubMed2000

Underutilization of breast-conserving therapy in a predominantly rural population: need for improved surgeon and public education.

Though breast-conserving therapy (BCT) was first recommended as the preferred treatment for women with early-stage breast cancer in 1990, little is known about the factors influencing or limiting the use of BCT in rural women. We retrospectively surveyed all surviving patients (227) referred to the Roger Maris Cancer Center over a 2-year period. Disease characteristics were verified by the tumor registry and random chart review. Responses were obtained from 171 patients (75%), a median of 26 months from diagnosis. The majority of patients were from rural areas; only 32% resided in towns with a population greater than or equal to 15,000. Thirty-five percent of those patients meeting published criteria had BCT. Patients who underwent BCT were younger (mean age 56.8 vs. 62.5, P = 0.01), more likely to have benign axillary lymph nodes (82% vs. 64%, P = 0.008), and more likely to be employed away from the home (66% vs. 44%, P = 0.01) than patients who underwent mastectomy (MRM). Distance from the nearest radiation facility did not affect treatment decisions (mean: 59.5 miles BCT vs. 52.6 miles MRM). Most patients (83%) ranked their surgeon as the most important source of information about treatment options. Perceived surgical recommendations were generally followed. Only three patients who felt their surgeon recommended MRM underwent BCT; eleven patients chose MRM though they believed their surgeon recommended BCT. The choice of local therapy is predominantly a surgeon-driven process; logistical barriers unique to a rural population had little impact. Unfortunately, many surgeons continue to apply much more stringent criteria when recommending BCT than those in published guidelines.

Adult↗
PubMed2000

Detection of indinavir crystals in urine: dependence on method of analysis.

OBJECTIVES: To determine the frequency of crystalluria in patients treated with the human immunodeficiency virus protease inhibitor indinavir and to compare methods of detecting crystalluria. METHODS: A total of 308 freshly voided urine specimens from 168 patients treated with indinavir were evaluated by manual microscopy of sediment and microscopy with an automated workstation and by dipstick analysis. RESULTS: Crystals were detected in 22%, 31%, or 32% of specimens using, respectively, an automated workstation, manual microscopy, or both methods. Proteinuria or hemoglobinuria occurred significantly more often in specimens with (28%) than without (18%) crystals. Frequency of crystalluria was unrelated to specific gravity, but it increased at higher pH. Crystals were detected in 21% of specimens with pH less than 6 and 42% of specimens with pH of 6 or higher. CONCLUSIONS: Crystalluria occurs in more than 30% of urine specimens from patients treated with indinavir, but detection rates vary substantially with method of analysis. Manual microscopy detected crystalluria 41% more often than did an automated workstation.

Crystallization↗
PubMed1999

HIV-1 and T cell dynamics after interruption of highly active antiretroviral therapy (HAART) in patients with a history of sustained viral suppression.

Identifying the immunologic and virologic consequences of discontinuing antiretroviral therapy in HIV-infected patients is of major importance in developing long-term treatment strategies for patients with HIV-1 infection. We designed a trial to characterize these parameters after interruption of highly active antiretroviral therapy (HAART) in patients who had maintained prolonged viral suppression on antiretroviral drugs. Eighteen patients with CD4(+) T cell counts >/= 350 cells/microliter and viral load below the limits of detection for >/=1 year while on HAART were enrolled prospectively in a trial in which HAART was discontinued. Twelve of these patients had received prior IL-2 therapy and had low frequencies of resting, latently infected CD4 cells. Viral load relapse to >50 copies/ml occurred in all 18 patients independent of prior IL-2 treatment, beginning most commonly during weeks 2-3 after cessation of HAART. The mean relapse rate constant was 0.45 (0.20 log(10) copies) day(-1), which was very similar to the mean viral clearance rate constant after drug resumption of 0.35 (0.15 log(10) copies) day(-1) (P = 0.28). One patient experienced a relapse delay to week 7. All patients except one experienced a relapse burden to >5,000 RNA copies/ml. Ex vivo labeling with BrdUrd showed that CD4 and CD8 cell turnover increased after withdrawal of HAART and correlated with viral load whereas lymphocyte turnover decreased after reinitiation of drug treatment. Virologic relapse occurs rapidly in patients who discontinue suppressive drug therapy, even in patients with a markedly diminished pool of resting, latently infected CD4(+) T cells.

Adult↗
PubMed1999

Purification, cloning, and heterologous expression of a catalytically efficient flavonol 3-O-galactosyltransferase expressed in the male gametophyte of Petunia hybrida.

Flavonols are plant-specific molecules that are required for pollen germination in maize and petunia. They exist in planta as both the aglycone and glycosyl conjugates. We identified a flavonol 3-O-galactosyltransferase (F3GalTase) that is expressed exclusively in the male gametophyte and controls the formation of a pollen-specific class of glycosylated flavonols. Thus an essential step to understanding flavonol-induced germination is the characterization of F3GalTase. Amino acid sequences of three peptide fragments of F3GalTase purified from petunia pollen were used to isolate a full-length cDNA clone. RNA gel blot analysis and enzyme assays confirmed that F3GalTase expression is restricted to pollen. Heterologous expression of the F3GalTase cDNA in Escherichia coli yielded active recombinant enzyme (rF3GalTase) which had the identical substrate specificity as the native enzyme. Unlike the relatively nonspecific substrate usage of flavonoid glycosyltransferases from sporophytic tissues, F3GalTase uses only UDP-galactose and flavonols to catalyze the formation of flavonol 3-O-galactosides. Kinetic analysis showed that the k(cat)/K(m) values of rF3GalTase, using kaempferol and quercetin as substrates, approaches that of a catalytically perfect enzyme. rF3GalTase catalyzes the reverse reaction, generation of flavonols from UDP and flavonol 3-O-galactosides, almost as efficiently as the forward reaction. The biochemical characteristics of F3GalTase are discussed in the context of a role in flavonol-induced pollen germination.

Amino Acid Sequence↗
PubMed1999

Lymph node architecture preceding and following 6 months of potent antiviral therapy: follicular hyperplasia persists in parallel with p24 antigen restoration after involution and CD4 cell depletion in an AIDS patient.

OBJECTIVES: To evaluate changes in architecture, viral RNA, and viral protein over 6 months in lymph nodes from retroviral-naïve HIV-infected persons before and after commencing highly active antiretroviral therapy (HAART). METHODS: Nine antiretroviral-naïve HIV-infected persons had lymph nodes excised at baseline and at 2 and 6-8 months after beginning a four-drug combination regimen containing zidovudine, lamivudine, nevirapine, and indinavir. Two patients had AIDS. Lymph nodes were examined by immunohistochemical staining for Gag p24 HIV, CD3, CD21, CD20, HAM 56, and Ki67 antigens and by in-situ hybridization (ISH) for HIV RNA and H3-histone RNA. RESULTS: Eight of nine baseline lymph nodes showed follicular hyperplasia and germinal center and paracortical mononuclear cell activation. At 2 months, the lymph nodes from seven patients, including the AIDS patients, showed more follicular hyperplasia and activation than their baseline specimens but with decreased mononuclear cell activation. By 6 months, seven lymph nodes were less hyperplastic and activated than their corresponding 2 month specimens. Combined ISH/immunohistochemical staining of baseline lymph nodes revealed productively infected T (CD3) and B (CD20) cells and macrophages (HAM56+). HIV RNA-positive mononuclear cells were infrequent at 2 months, and rare at 6 months. HIV RNA was still associated with follicular dendritic cells (FDC) at 2 months, but not at 6 months. HIV p24-positive antigen in germinal centers persisted through all 6, and the one 8 month specimens. The baseline lymph nodes from one of the AIDS patients was involuted and T cell depleted, whereas the follow-up lymph nodes were hyperplastic with normal T cell levels. CONCLUSION: Follicular hyperplasia and cell activation, possibly caused by persistent viral protein in germinal centers, may help explain why HIV viremia rebounds so rapidly after the interruption of HAART. Restoration of architecture may follow the treatment of patients with AIDS who initially had involuted and CD4 cell-depleted lymph nodes.

Acquired Immunodeficiency Syndrome↗
PubMed1999

The subregion correspondence model of binocular simple cells.

We explore the hypothesis that binocular simple cells in cat areas 17 and 18 show subregion correspondence, defined as follows: within the region of overlap of the two eye's receptive fields, their ON subregions lie in corresponding locations, as do their OFF subregions. This hypothesis is motivated by a developmental model (Erwin and Miller, 1998) that suggested that simple cells could develop binocularly matched preferred orientations and spatial frequencies by developing subregion correspondence. Binocular organization of simple cell receptive fields is commonly characterized by two quantities: interocular position shift, the distance in visual space between the center positions of the two eye's receptive fields; and interocular phase shift, the difference in the spatial phases of those receptive fields, each measured relative to its center position. The subregion correspondence hypothesis implies that interocular position and phase shifts are linearly related. We compare this hypothesis with the null hypothesis, assumed by most previous models of binocular organization, that the two types of shift are uncorrelated. We demonstrate that the subregion correspondence and null hypotheses are equally consistent with previous measurements of binocular response properties of individual simple cells in the cat and other species and with measurements of the distribution of interocular phase shifts versus preferred orientations or versus interocular position shifts. However, the observed tendency of binocular simple cells in the cat to have "tuned excitatory" disparity tuning curves with preferred disparities tightly clustered around zero (Fischer and Krüger, 1979; Ferster, 1981; LeVay and Voigt, 1988) follows naturally from the subregion correspondence hypothesis but is inconsistent with the null hypothesis. We describe tests that could more conclusively differentiate between the hypotheses. The most straightforward test requires simultaneous determination of the receptive fields of groups of three or more binocular simple cells.

Animals↗
PubMed1999

Is the development of orientation selectivity instructed by activity?

Is the development of orientation selectivity in visual cortex instructed by the patterns of neural activity of input neurons? We review evidence as to the role of activity, review models of activity-instructed development, and discuss how these models can be tested. The models can explain the normal development of simple cells with binocularly matched orientation preferences, the effects of monocular deprivation and reverse suture on the orientation map, and the development of a full intracortical circuit sufficient to explain mature response properties including the contrast-invariance of orientation tuning. Existing experiments are consistent with the models, in that (a) selective blockade of ON-center ganglion cells, which will degrade or eliminate the information predicted to drive development of orientation selectivity, in fact prevents development of orientation selectivity; and (b) the spontaneous activities of inputs serving the two eyes are correlated in the lateral geniculate nucleus at appropriate developmental times, as was predicted to be required to achieve binocular matching of preferred orientations. However, definitive tests remain to be done to firmly establish the instructive rather than simply permissive role of activity and determine whether the retinotopically and center type-specific patterns of activity predicted by the models actually exist. We conclude by critically examining alternative scenarios for the development of orientation selectivity and maps, including the idea that maps are genetically prespecified.

Animals↗
PubMed1999

The role of chemotherapy for metastatic breast cancer.

Metastatic breast cancer remains a devastating and largely incurable disease. Currently available therapies offer meaningful palliation for many and modest prolongation of survival for some patients. Single-agent hormonal therapy remains the treatment of choice for patients with ER-positive disease, with sequential use of further hormonal agents or cytotoxic chemotherapy at the time of disease progression. Chemotherapy is appropriate as initial therapy for patients with receptor-negative or rapidly progressive visceral disease. Although combination regimens may increase response rates, the lack of survival benefit does not justify the increased toxicity of aggressive combination regimens in most patients. Maintenance chemotherapy deserves consideration in selected well-informed patients, especially those with few therapy-related side effects. High-dose regimens confer substantial toxicity with no clear therapeutic advantage and cannot be recommended outside of ongoing trials. New chemotherapy agents offer the hope of effective salvage therapy with acceptable toxicity to a larger number of patients. Perhaps most promising, the development of targeted, biologically based therapies such as rhuMAbHER2 offers encouragement for the future.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1999

Toward checkmate: biology and breast cancer therapy for the new millennium.

A better understanding of the biology of breast cancer should lead to the rational development of new treatments and the ability to customize therapy for individual patients. Though promising in theory, translating advances in biological knowledge to the clinic has been difficult. Recently several areas of research have produced treatments which have entered clinical trials: three will be reviewed here. The growth of breast cancer is regulated by growth factors and their receptors; amplification or overexpression is associated with poor prognosis. As such inhibition of growth factors and/or growth factor receptors may provide an ideal therapeutic target. Herceptin binds to c-erbB-2, a member of the epidermal growth factor receptor family. Significant responses were seen in patients with c-erbB-2 overexpressing breast cancer with Herceptin administered as a single agent or in combination with chemotherapy. Herceptin was approved by the Food and Drug Administration in late 1998. Breast cancer invasion and metastasis requires degradation of the surrounding basement membrane by matrix metalloproteinases and other proteolytic enzymes. Synthetic inhibitors of these enzymes are now in clinical trials. Breast cancers must stimulate angiogenesis, the growth of new blood vessels, in order to grow beyond a few millimeters in diameter. This nascent vascular network provides another opportunity for therapy. Preclinical models support the critical role of angiogenesis and the therapeutic benefit of angiogenesis inhibition; clinical trials are underway.

Animals↗
PubMed1999

Immunostaining for cyclin D1 and the diagnosis of mantle cell lymphoma: is there a reliable method?

Immunostaining for cyclin D1 has become essential for the reliable diagnosis of mantle cell lymphoma (MCL). MCL is associated with a poor prognosis and its distinction from other small B-cell lymphomas is clinically important. However, many diagnostic laboratories report problems in finding a reliable method. The following articles by Chan and by Miller, Munson & Isaacson discuss the common problems and describe successful methods with advice on diagnostic interpretation.

Cyclin D1↗
PubMed1999

Hepatitis G virus and human immunodeficiency virus coinfection: response to interferon-alpha therapy.

The prevalence and consequences of hepatitis G virus (HGV) infection were determined in 180 patients with human immunodeficiency virus (HIV) infection (predominantly male homosexuals) who participated in a trial that compared treatment with zidovudine versus interferon (IFN)-alpha versus the combination. HGV RNA levels were measured by branched DNA signal amplification assay. Initially, 66 (37%) had HGV RNA. Sexual transmission was the sole risk factor for infection in all but 4 subjects. Pretreatment clinical features were similar between HGV RNA-positive and -negative patients. After 6 months, only 5% treated with zidovudine became HGV RNA negative, compared with 95% who received IFN-alpha alone and 66% on combination therapy with low-dose IFN-alpha. After therapy, HGV RNA levels returned to baseline in most subjects. Thus, HGV infection is common among HIV-infected homosexual males but does not appear to influence clinical features in early HIV infection. HGV RNA levels are suppressed by IFN but not by zidovudine.

Adult↗
PubMed1999

Increased pyramidal excitability and NMDA conductance can explain posttraumatic epileptogenesis without disinhibition: a model.

Partially isolated cortical islands prepared in vivo become epileptogenic within weeks of the injury. In this model of chronic epileptogenesis, recordings from cortical slices cut through the injured area and maintained in vitro often show evoked, long- and variable-latency multiphasic epileptiform field potentials that also can occur spontaneously. These events are initiated in layer V and are synchronous with polyphasic long-duration excitatory and inhibitory potentials (currents) in neurons that may last several hundred milliseconds. Stimuli that are significantly above threshold for triggering these epileptiform events evoke only a single large excitatory postsynaptic potential (EPSP) followed by an inhibitory postsynaptic potential (IPSP). We investigated the physiological basis of these events using simulations of a layer V network consisting of 500 compartmental model neurons, including 400 principal (excitatory) and 100 inhibitory cells. Epileptiform events occurred in response to a stimulus when sufficient N-methyl-D-aspartate (NMDA) conductance was activated by feedback excitatory activity among pyramidal cells. In control simulations, this activity was prevented by the rapid development of IPSPs. One manipulation that could give rise to epileptogenesis was an increase in the threshold of inhibitory interneurons. However, previous experimental data from layer V pyramidal neurons of these chronic epileptogenic lesions indicate: upregulation, rather than downregulation, of inhibition; alterations in the intrinsic properties of pyramidal cells that would tend to make them more excitable; and sprouting of their intracortical axons and increased numbers of presumed synaptic contacts, which would increase recurrent EPSPs from one cell onto another. Consistent with this, we found that increasing the excitability of pyramidal cells and the strength of NMDA conductances, in the face of either unaltered or increased inhibition, resulted in generation of epileptiform activity that had characteristics similar to those of the experimental data. Thus epileptogenesis such as occurs after chronic cortical injury can result from alterations of intrinsic membrane properties of pyramidal neurons together with enhanced NMDA synaptic conductances.

Animals↗
PubMed1999

Combination versus sequential doxorubicin and docetaxel as primary chemotherapy for breast cancer: A randomized pilot trial of the Hoosier Oncology Group.

PURPOSE: To evaluate the efficacy and toxicity of combination and sequential dose-dense chemotherapy with doxorubicin and docetaxel (Taxotere; Rhône-Poulenc Rorer, Collegeville, PA) as primary chemotherapy of breast cancer. PATIENTS AND METHODS: Patients with newly diagnosed stage II or noninflammatory stage III breast cancer were randomly assigned to receive the same total doses of doxorubicin and docetaxel over a 12-week period before definitive surgery. Patients in arm A received sequential therapy with doxorubicin 75 mg/m(2) every 2 weeks for three cycles followed by docetaxel 100 mg/m(2) every 2 weeks for three cycles. Patients in arm B received combination therapy with doxorubicin 56 mg/m(2) plus docetaxel 75 mg/m(2) every 3 weeks for four cycles. Granulocyte colony-stimulating factor was administered on days 2 to 12 of each cycle in both groups. RESULTS: Forty patients were entered onto the trial. Pretreatment tumor size averaged 5.7 cm with clinically positive axillary lymph nodes in 23 patients (57%). As expected, myelosuppression was severe in both groups; however, >/= 80% of planned dose-intensity was delivered. Hand-foot syndrome was more common after sequential therapy. Clinical responses were similar in both groups, with an overall response rate of 87%, including 20% clinical complete remissions. Pathologic complete remission or residual in situ disease only was confirmed in five patients (12.8%). Patients who received sequential therapy had fewer positive lymph nodes (mean, 2.17 v 4.81; P <.037) at definitive surgery. CONCLUSION: Primary chemotherapy with doxorubicin and docetaxel is well tolerated and highly active. A sequential treatment schedule increases toxicity but may result in more substantial lymph node clearance than combination therapy.

Adult↗