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Biomedical subjects

W J Miller

Publications and source records attributed to W J Miller.

At least 91 records · Page 5Linked to original sources
PubMed1991

Varicella vaccine (VARIVAX) in healthy children and adolescents: results from clinical trials, 1987 to 1989.

A total of 3303 healthy children and adolescents, aged 12 months to 17 years, were vaccinated with one of five production lots of a live attenuated varicella vaccine (VARIVAX) containing 1000 to 1625 plaque-forming units per dose. The vaccine was generally well tolerated. Ninety-six percent (2381/2475) of vaccinees responded to vaccination by producing antibody as measured by a glycoprotein-based enzyme-linked immunosorbent assay; 99% (569/576) of those tested maintained antibody at 1 year following vaccination. The incidence of varicella following household exposure in vaccinees was approximately 12%; household contact historically results in 87% infection. Nearly all of the vaccinees who had varicella after vaccination had a clinically modified disease.

Adolescent↗
PubMed1991

Autologous bone marrow transplantation for progressive non-Hodgkin's lymphoma: clinical impact of immunophenotype and in vitro purging.

From 1983 to 1989 we performed a prospective trial of 70 consecutive, in vitro purged autologous bone marrow transplants (BMT) for patients with progressive non-Hodgkin's lymphoma. Forty-nine patients had responsive disease at the time of transplantation while 21 others had refractory high risk lymphoma. Forty-two patients with B-lineage lymphoma received autologous marrow purged in vitro with monoclonal antibody (anti CD9, CD10, CD24) plus complement, 12 with T-lineage lymphoma received monoclonal antibody immunotoxins (anti CD5, CD7-ricin conjugates) along with 4-hydroperoxycyclophosphamide purging and 16 received unpurged marrow. All received cyclophosphamide, 57 with fractionated total body irradiation, and 13 with BCNU and cytarabine. Hematologic engraftment was prompt and unaffected by phenotype (B vs. T) or by in vitro purging used (B vs. T vs. none) although nine of 16 non-relapse deaths were related to poor graft function. Fifty-one patients (73%) were alive in complete remission (CR) 1 month following transplantation while 15 patients (12 with initially refractory disease) had persistent disease. Subsequently, 41 +/- 18% (by Kaplan-Meier estimate; +/- 95% confidence limits) of those who achieved CR remained relapse free 1-6.4 (median 3) years post-BMT. Neither risk group, purging, nor immunophenotype predicted subsequent post-transplant relapse. Among those 51 who achieved CR, 13 of 43 (27 +/- 14%) with responsive disease survive disease free while three of eight (38 +/- 34%) refractory patients survive disease free (p = 0.96). Overall, 24 patients survive, 16 in continuous complete remission 1-6.5 years following transplantation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1990

Acute upper gastrointestinal graft-versus-host disease: clinical significance and response to immunosuppressive therapy.

Recognized manifestations of acute graft-versus-host disease (GVHD) of the gastrointestinal (GI) tract include secretory diarrhea, abdominal pain, and, at times, hemorrhage. In a review of 469 patients undergoing allogeneic bone marrow transplantation (BMT) from matched sibling donors at our institution, we have recognized a syndrome of upper GI GVHD. This syndrome, presenting clinically as anorexia, dyspepsia, food intolerance, nausea, and vomiting, was recognized and confirmed histologically in 62 patients (13% by Kaplan-Meier projection) at the initiation of systemic GVHD therapy, a subset of the 197 patients developing grade II through IV GVHD. These 62 patients with upper GI GVHD were significantly older than the overall BMT population and older than the cohort with grade II through IV GVHD, as well. Of the 62 patients, 25 had upper GI GVHD accompanied only by limited (stage 1 and 2) skin GVHD; 13 others with upper GI GVHD plus limited skin involvement at initial presentation later progressed to more extensive multiorgan involvement; 24 others presented with upper GI along with other organ GVHD. This upper GI GVHD syndrome, first recognized at our center in 1983, has been diagnosed with increasing frequency (22% +/- 5%) in the most recent 5-year interval. The upper GI GVHD syndrome is more responsive to immunosuppressive therapy than grade II GVHD defined by Seattle criteria, with complete and continuing responses to treatment observed in 71% +/- 17% (95% confidence interval) of those with the upper GI GVHD syndrome compared with only 37% +/- 10% complete responses in other patients with grade II GVHD (P = .002). Patients failing immunosuppressive therapy for upper GI GVHD often progress to symptomatic lower GI involvement, suggesting that this syndrome may be an earlier and perhaps more treatable manifestation of this unique intestinal immunopathology, which is followed by chronic GVHD in 74% of patients. While upper GI GVHD symptoms are nonspecific and require invasive histologic and microbiologic studies to confirm the diagnosis, we believe this syndrome has been underreported after allogeneic BMT and propose its recognition within the clinical GVHD scoring system.

Acute Disease↗
PubMed1990

Anti-PreS2 antibody assay for evaluating immune responses among recipients of recombinant hepatitis B PreS2 + S vaccine.

A competitive radioimmunoassay was developed for measuring hepatitis B virus (HBV) anti-PreS2 antibody. The assay has been demonstrated to be highly specific for anti-PreS2 antibody and not subject to interference by other antibodies to HBV-specific antigens. This assay was used to evaluate anti-PreS2 antibody responses in a hepatitis B PreS2 + S vaccine human clinical trial in healthy adults.

Animals↗
PubMed1990

Sensitive enzyme-linked immunosorbent assay for antibody to varicella-zoster virus using purified VZV glycoprotein antigen.

The development of an ELISA of increased sensitivity has permitted a more critical evaluation of human humoral immune responses to the live attenuated varicella (Oka/Merck) vaccine. For use as a solid-phase antigen, the glycoprotein (gp) antigens are prepared by lectin-affinity chromatography from lysates of VZV-infected MRC-5 cells. The lot-to-lot variation in VZV gp content is controlled by standardization of antigen against a panel of human serum providing antigen-coated plates of consistent quality. The increased sensitivity of the gpELISA over the VAR ELISA is reflected in the greater seroconversion rate and prepositive rate specificity. These determinations have been shown to be specific for anti-VZV by absorption experiments using purified VZV gp antigens.

Antibodies, Viral↗
PubMed1990

P-related sequences in Drosophila bifasciata: a molecular clue to the understanding of P-element evolution in the genus Drosophila.

Two P-elements (bif1 and bif2) were isolated from a genomic library of Drosophila bifasciata. Both elements are internally deleted and have lost the coding capacity for a functional transposase. One of the elements (bif2) contains an insert consisting of a repetitive sequence. The terminal inverted repeats and the segments necessary for passive mobility are well conserved. Element bif2 has retained rudiments of the coding sequence of exon 0 and exon 3, but the reading frame is destroyed by insertions and deletions. The comparison of the D. bifasciata P-elements with P-elements of Drosophila melanogaster and Drosophila nebulosa reveals that the two latter sequences are more similar to each other than either of them is to the D. bifasciata elements. This finding contradicts the phylogenetic relationship of the species and can be taken as an indirect but unequivocal evidence for recent horizontal gene transfer from a relative of D. nebulosa to the gene pool of D. melanogaster. The P-elements of D. bifasciata are phylogenetically ancient and have evolved independently for about 50 million years. A higher substitution rate at the third codon position as well as a predominance of conservative replacements at the amino acid level indicates that the P-elements of D. bifasciata have been under selective constraint over a long period and that immunobilization has occurred only recently.

Amino Acid Sequence↗
PubMed1990

In vitro immune responses to hepatitis B surface antigens S and preS2 during acute infection by hepatitis B virus in humans.

This study evaluated the in vitro immune responses to different components of the hepatitis B surface antigen (HBsAg) over the course of acute hepatitis B virus (HBV) infection. Early in the convalescent phase of infection, while HBsAg was present in the serum, peripheral blood mononuclear cells (PBMCs) were stimulated with preS2 peptide or hepatitis B surface protein. Specific IgG directed to different components of HBsAg was produced without a polyclonal increase in total IgG production. Stimulation with preS2 peptide produced IgG to the preS2 peptide (anti-preS2) and to the S antigen (anti-HBs). Hepatitis B surface protein stimulation produced anti-HBs but not anti-preS2. After this initial reactive phase, the PBMCs did not produce specific antibody when stimulated with either component of HBsAg; this effect lasted greater than 1 year. At some time 1-2 years after acute infection, the pattern of in vitro S antigen- and preS2 antigen-stimulated anti-HBs response reemerged in the PBMCs. Reemergence of sustained preS2 peptide-stimulated anti-preS2 response was not observed.

Cells, Cultured↗
PubMed1990

Influence of dietary aluminum and phosphorus on zinc metabolism in dairy calves.

The metabolism of a single oral zinc-65 dose was studied in young dairy calves fed two concentrations of added A1 (0 and .20% A1) and two concentrations of added P (0 and .22% P) for 7 wk. The four treatments were 1) normal P-low A1, 2) low P-low A1, 3) normal P-high A1 and 4) low P-high A1. The basal diet (low P-low AL) contained, by analysis, .132% P, .74% Ca, .021% A1 and 59 ppm Zn. Zinc-65 absorption was greater (66.5 vs 63.2% of dose, P less than .10) with the low-P diet; added A1 reduced (P less than .05) 65Zn absorption. Calves fed low-P diets had higher (P less than .10) concentrations of 65Zn in liver, kidney, spleen, heart, small intestine and testicle than those fed normal-P diets. Zinc-65 was reduced (P less than .10) in pancreas, heart, testicle and muscle of calves fed high A1. Iron was increased in liver and kidney (P less than .10), Zn (P less than .10) and Mn (P less than .01) were increased in liver, but Fe in small intestine and Cu in muscle and tibia shaft were decreased (P less than .10) in calves fed the low-P diets compared to those fed adequate-P diets. High A1 reduced (P less than .10) Cu in small intestine and tibia shaft. The results suggest that zinc metabolism may be moderately affected in calves fed either low-P or high-A1 diets.

Aluminum↗
PubMed1990

Effects of dietary aluminum and phosphorus on magnesium metabolism in dairy calves.

The metabolism of Mg was studied in young dairy calves fed two levels of added Al (0 and .20% Al) and two levels of added P (0 and .22% P) for 7 wk. The four treatments were 1) normal P-low Al, 2) low P-low Al, 3) normal P-high Al and 4) low P-high Al. The basal diet (low P-low Al) contained, by analysis, .132% P, .021% Al and .17% Mg. Added Al did not affect (P greater than .10) serum Mg. An Al x P interaction on bone Mg was detected (P less than .01). Magnesium was reduced in tibia shaft (.34 vs .44%) and in tibia joint (.43 vs .53%) in calves fed high Al in the presence of normal dietary P, but Mg was not reduced in the calves fed low-P diets. Apparent absorption of Mg was reduced by approximately five-fold (.18 g/d vs -.84 g/d, P less than .01); urinary Mg excretion was reduced 31% (1.12 g/d vs .77 g/d, P less than .01); and Mg retention declined 41% (-95 g/d vs -1.61 g/d, P less than .01) in calves fed added A1. Compared with calves fed low-P diets, calves fed normal levels of P had a higher Mg concentration in tibia shaft (P less than .01) and tibia joint (P less than .05). The data indicate that supplemental Al may adversely affect Mg metabolism in calves.

Alkaline Phosphatase↗
PubMed1990

Influence of high dietary aluminum on performance and phosphorus bioavailability in dairy calves.

Sixteen male intact Holstein calves averaging 72 kg and 64 d of age were used to study the effects of high dietary Al on calf performance and P bioavailability. The main effects were two concentrations of added aluminum (0 and .20% Al) and two of added P (0 and .22% P). The basal diet contained, by analysis, .132% P, .74% Ca, and .021% Al. The calves were assigned to four treatment groups balanced according to body weight. The four treatments were 1) normal P, low Al; 2) low P, low Al; 3) low P, high Al; and 4) normal P, high Al. Calved had ad libitum access to their respective diets for 7 wk. Metabolism of a single oral 32P dose was determined during wk 6. The adverse effects of high dietary Al include a 17% reduction in feed intake and a 47% reduction in body weight gains. Alkaline phosphatase and plasma glutamic oxaloacetate transaminase activities increased in calves receiving the high Al diets. A negative balance of P and Ca was noted in the calves fed high concentrations of Al. Apparent absorption of 32P was reduced (37%) in calved fed diets high in Al (44% of dose vs. 69%). Urinary excretion of 32P was not affected by dietary Al concentrations. Calves fed the low P (deficient) diet showed significant reductions in feed intake, weight gain, serum inorganic P, bone ash, and P content of bone. Dietary P did not significantly affect 32P absorption. Adding .20% dietary Al severely affects P metabolism and performance of young growing calves.

Aluminum↗
PubMed1990

Effects of high dietary lead on the metabolism of intravenously dosed selenium-75 in dairy calves.

The metabolism of intravenously dosed 75Se was studied in 10 Holstein bull calves fed for ad libitum access a control diet containing no added Pb or a control diet supplemented with 1000 ppm Pb as PbSO4 for 4 wk. The Pb-supplemented calves exhibited no clinical signs often ascribed to lead toxicity. Likewise, feed intake and body weight gains were not affected adversely. The lead content of rib, kidney, liver, and brain was increased. Serum glutamic oxaloacetate transaminase activity increased in the calves fed Pb during the last 2 wk of the experiment. The kidneys of the calves supplemented with lead were 34% larger than those of controls. The total endogenous 75Se in the feces over the 4-d collection period was not different between treatments (4.14% of dose versus 3.31% of dose). Likewise, urinary 75Se excretion values were similar. About 97% of the 75Se dose disappeared from the blood within 6 h after dosing four calves on both treatments. Tissue concentrations of 75Se were reduced in kidney, spleen, pancreas, brain, and spinal cord. In summary, ingested Pb had very little effect on the endogenous excretion of 75Se in urine and feces; therefore, the data are consistent with earlier research in which the main effect of Pb on Se occurs at the absorption site.

Animals↗
PubMed1990

Strategies for appeals of PRO payment denials.

Review of care furnished to Medicare patients by peer review organizations often results in denials of payment for services found not to be "covered" by the Medicare program. Providers should be aware that they can appeal these denials of payment, and that, at least at present, there is a good chance that such denials can be reversed on appeal.

Financial Management, Hospital↗
PubMed1990

Autologous transplantation for CML using marrow treated ex vivo with recombinant human interferon gamma.

Six chronic and four advanced patients with Ph1 positive chronic myelogenous leukemia (CML) received autologous bone marrow transplantation (ABMT) using bone marrow treated ex vivo with recombinant human interferon gamma (rIFN gamma). In three cases 100% Ph1 negative bone marrow hematopoiesis was demonstrated 4 to 8 weeks after ABMT. In three additional cases, a maximum of 40-45% bone marrow metaphases were Ph1 negative 2 to 12 weeks following ABMT. In four cases, no or minimal evidence of Ph1 negative hematopoiesis could be demonstrated posttransplant. Seven patients survive in chronic phase at a median of 375 days (range 100-495 days). Five patients have not required therapy, while two patients receive low doses of rIFN alpha to control peripheral blood counts. Ex vivo treatment of CML bone marrow with rIFN gamma followed by ABMT in patients dependent upon or refractory to therapy prior to transplantation is associated with transient complete or partial Ph1 negative bone marrow hematopoiesis in the majority of patients post-transplant and with return of a chronic phase characterized by no need for therapy or by response to low doses of rIFN alpha. Modification of the ABMT procedure and efforts to maintain cytogenetic and hematologic remission following ABMT may lead to prolonged survival or cure.

Adult↗
PubMed1989

Mature T-lineage leukemia with growth factor-induced multilineage differentiation.

We report an acute T-lymphoblastic leukemia with a predominantly mature CD3+ CD7+ WT31+ phenotype that was induced to differentiate into different cell lineages by various recombinant human growth factors. In the presence of IL-3 or GM-CSF, the leukemic cells gave rise to myeloid and monocytic cells including terminally differentiated, partially functional, segmented neutrophilic granulocytes as assessed by morphologic, cytochemical, immunophenotypic, and functional criteria. In the presence of IL-2, leukemic granulated lymphoid cells exhibiting MHC-unrestricted cytotoxicity and expressing a CD2+ CD3+ CD5+ CD7+ CD8+ CD33+ WT31+ Leu19+ phenotype arose. Leukemic cell cultures initiated with IL-3 yielded growth factor-independent cells with a mixed lineage phenotype and morphologic and cytochemical evidence of immature blasts. These were T lymphocyte and myeloid surface antigen (CD2,CD3,CD5,CD7,CD13,CD33,WT31) positive. Identical rearrangements of the constant region of the TCR-delta gene and of the joining regions of the TCR-beta, -gamma, and -delta genes were observed in the fresh and all cultured leukemic cells, indicating that they were derived from the same malignant clone. Consistent with the molecular genetic data, the cytogenetic analyses of the GM-CSF-, IL-3-cultured and the growth factor-independent leukemic cells showed the presence of multiple, closely related abnormal clones, all of which had an interstitial deletion of part of the long arm of chromosome 6 and a complex 1;10;12 translocation. In conclusion, these data demonstrate the involvement of a multipotent leukemic precursor cell in this predominantly mature CD2+ CD3+ CD5+ CD7+ WT31+ T-ALL. This multipotent leukemic precursor may be susceptible to various growth factors and respond with ordered differentiation and maturation.

Adult↗
PubMed1989

Protective effect of a synthetic peptide comprising the complete preS2 region of the hepatitis B virus surface protein.

A peptide was synthesized containing the entire 55 amino acid residue sequence of the hepatitis B virus (HBV) surface antigen preS2 region (ad subtype). The unconjugated peptide was inoculated into four chimpanzees. Following multiple injections, all of the animals developed specific antipeptide antibodies that reacted with intact surface antigen particles bearing the preS2 moiety. All four peptide-inoculated animals were found to be protected from infection after intravenous challenge with live HBV of either the ad or ay subtypes.

Animals↗
PubMed1989

In vitro immune responses to hepatitis B surface antigen (Pre-S2 and S) following remote infection by hepatitis B virus in humans.

In this report we evaluate the human immune response to hepatitis B surface antigen (HBsAg) following remote infection with hepatitis B virus (HBV). HBsAg-reactive lymphocytes can be readily demonstrated in the peripheral blood of individuals with established immunity following infection with HBV. In vitro stimulation with small doses of plasma-derived HBsAg, yeast-derived HBsAg (S region) or pre-S2 peptide will induce specific IgG to HBsAg (anti-HBs) in the absence of a polyclonal increase in total IgG. The pre-S2 peptide will stimulate, in a T cell-dependent fashion, the in vitro production of anti-HBs with specificity for the S domain. This anti-HBs production is mediated by pre-S2-stimulated soluble T-cell factors. Peripheral blood mononuclear cells from individuals with established immunity proliferate to the yeast-derived HBsAg but not to the plasma-derived HBsAg or pre-S2 peptide. The chronic HBsAg carriers do not produce anti-HBs following stimulation with HBsAg regardless of the source or component of antigen used. Different study protocols failed to demonstrate HBsAg-specific responses in the peripheral blood mononuclear cells of chronic carriers.

Adult↗