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W M Miller

Publications and source records attributed to W M Miller.

78 records · Page 5Linked to original sources
PubMedDate not supplied

Role of nucleotide sugar pools in the inhibition of NCAM polysialylation by ammonia.

Ammonia in animal cell cultures has been shown to specifically inhibit terminal sialylation of N- and O-linked oligosaccharides of glycoproteins. For example, we have previously shown that as little as 2.5 mM NH4Cl can decrease neural cell adhesion molecule (NCAM) polysialylation in both small cell lung cancer (SCLC) and Chinese hamster ovary (CHO) cells. Besides its potential involvement in SCLC metastasis, polysialic acid (PolySia) is a sensitive marker for measuring changes in sialylation. The role of UDP-N-acetylglucosamine (UDP-GlcNAc) in ammonia's inhibition of NCAM polysialylation was examined by adding glucosamine (GlcN) and uridine (Urd) to the cultures. This bypassed feedback inhibition of GlcN-6-P synthase and increased UDP-GlcNAc content by 25-fold in SCLC cells. After 3 days, PolySia levels were reduced to 10% of control with little effect on NCAM protein content. The extensive decrease in PolySia was confirmed in CHO cells. The effects of GlcN or Urd alone were less extensive, lending support to a specific role for UDP-GlcNAc in inhibition by ammonia. By comparison, 20 mM NH4Cl decreased PolySia content by 45% and increased UDP-GlcNAc in SCLC cells by 2-fold. The discrepancy between the ¿GlcN+Urd¿ and NH4Cl effects on UDP-GlcNAc and PolySia suggests that accumulation of UDP-GlcNAc is only partially responsible for decreased polysialylation in response to NH4Cl. In an attempt to increase NCAM polysialylation, N-acetylmannosamine and cytidine were added to cultures in order to circumvent the feedback inhibition of CMP-sialic acid synthesis. However, this only slightly increased PolySia levels and failed to counter ammonia's inhibition of NCAM polysialylation.

Ammonia↗
PubMedDate not supplied

Terminal-deoxynucleotidyl transferase (TdT): serial observations on patients with leukemia.

Terminal-deoxynucleotidyl transferase (TdT) bone marrow determinations were performed on 67 patients with leukemia using the indirect immunofluorescence technique. A total of 103 smears were evaluated on 32 patients with acute lymphoblastic leukemia. With some exceptions, TdT levels were elevated at onset, declined during induction except in resistant cases, decreased during remission on chemotherapy, showed slight elevation during remission off chemotherapy, and rose during relapse in those cases previously positive. The most important finding was that patients in remission may have elevated TdT levels. Those were usually less than 10%. A total of 124 bone marrow smears were evaluated on 29 patients with acute myeloid leukemia. In general, values in all categories were below 1%, with a few elevated between 1% to 10%. Six patients with chronic myelogenous leukemia in blast crisis had 13 bone marrow smears evaluated. Five were in myeloblastic crisis and had values of less than 1%; 1 was lymphoblastic which had 50% positive cells at onset. In our experience, TdT determinations are of value in lymphoblastic leukemia in diagnosis, in predicting response to therapy, and in detecting early relapse.

Adolescent↗
PubMedDate not supplied

The AutoPap system for primary screening in cervical cytology. Comparing the results of a prospective, intended-use study with routine manual practice.

OBJECTIVE: To evaluate the effectiveness of the AutoPap System in detecting abnormal and normal cervical smears when used in a primary screening/quality control mode, as compared with currently established laboratory practices. STUDY DESIGN: Slides were obtained prospectively and were initially processed in the routine fashion with cytotechnologist screening followed by 10% random quality control rescreening. Slides were then processed on the AutoPap System and allocated into the following groups: (1) approximately 25% of the lowest-ranking slides were placed in the laboratory's archives as within normal limits; (2) the remaining approximately 75% of slides were subjected to manual screening. Approximately 15% of the highest-ranking slides in this group underwent quality control rescreening. For each slide needing manual screening, the cytotechnologist was supplied with a report giving the ranking score of that slide. All discrepant slides for either adequacy or diagnosis were subjected to a truth-determination process. The results obtained from the two arms of the protocol were then compared. RESULTS: The AutoPap System-assisted arm of the study was superior to the current practice arm for the identification of abnormal slides at the level of atypical squamous cells of undetermined significance and above (ASCUS+), low grade squamous intraepithelial lesion (LSIL) and higher LSIL+. AutoPap System-assisted practice was equivalent to current practice for the identification of unsatisfactory and satisfactory but limited by slides. All results showed statistical significance. In addition, AutoPap System-assisted practice in the study indicated improved specificity of diagnosis. CONCLUSION: AutoPap System-assisted practice shows superior sensitivity and specificity when compared to current practice. Its clinical use as a primary screening device should improve the overall practice of cervical cytology as well as provide potential enhancement in overall laboratory productivity.

Algorithms↗
PubMedDate not supplied

Diabetic foot amputations. Part III: Midfoot.

Recently, the approach in management of diabetic foot disorders has undergone critical re-evaluation. Major foot infections, such as plantar space infections and osteomyelitis do not automatically result in Syme's or below-the-knee amputations. When indicated, midfoot amputations should be attempted because of the functional and psychologic advantages compared with more proximal amputation levels of the lower extremity. In Part III of this series of articles concerning diabetic foot amputations, the authors present case studies along with midfoot amputations and muscle-balancing procedures.

Aged↗
PubMedDate not supplied

Anemia in women ages 20 to 89 years: rationale and tools for differential diagnosis.

Anemia is an underdiagnosed condition warranting intensified screening efforts. By conducting more systematic laboratory testing and by obtaining more interpretive test reports, physicians can greatly improve their recognition, diagnosis, and management of anemic patients. One way to improve the diagnosis and ultimate treatment of anemia is to categorize the condition using two parameters in the blood count--red blood cell size, measured as mean corpuscular volume (MCV), and variability of red blood cell size (anisocytosis), determined by red cell volume distribution width (RDW). Our study of anemic women aged 20 to 89 years examined the two parameters of RDW and MCV. Based on the anemia classification scheme devised by J.D. Bessman et al, the red cells of all of the patients studied were categorized as follows: heterogeneous microcytic (HTMI), homogeneous microcytic (HMMI), heterogeneous normocytic (HTN), homogeneous normocytic (HMN), heterogeneous macrocytic (HTMA), or homogeneous macrocytic (HMMA). HMN anemia, often linked with the anemia of chronic disease, was the most common type in all age groups, representing 60% to 76% of all cases of anemia. HTMI anemia occurred most frequently in women between the ages of 30 and 49 years, an expected finding. The HTN and HMMA anemias occurred somewhat more frequently in older patients. Through an initial classification of anemia based on MCV and RDW, the clinician has the groundwork for further testing that will lead to a diagnosis.

Adult↗