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Biomedical subjects

L Miller

Publications and source records attributed to L Miller.

At least 325 records · Page 18Linked to original sources
PubMed1987

Compartmentalization of cells bearing "rheumatic" cell surface antigens in peripheral blood and tonsils in rheumatic heart disease.

Monoclonal antibodies that recognize "rheumatic" antigens of peripheral blood non-T cells were used to study the compartmentalization of such cells in peripheral blood and tonsils of individuals with rheumatic heart disease (RHD) and suitable control subjects. The peripheral blood of most (71%) of the 42 individuals with RHD contained cells reacting with monoclonal antibody 83S19.23 or 256S.10, whereas these cells were present in only 17% of the 41 control subjects (P less than .02). However, none of 21 individuals with RHD had such cells in their tonsils, although they were present in the tonsils of 50% of the 40 control subjects (P less than .03). These results may reflect a failure in RHD or organ-specific homing of cells with the epitopes recognized by the antibodies. The presence of these cells in tonsils may be important in the immune response to streptococcal pharyngeal infection, and their absence in RHD may be involved in the unusual immune responses characteristic of this disease.

Adolescent↗
PubMed1987

Thyroid hormone induction of keratin genes: a two-step activation of gene expression during development.

To determine the mechanism of action of the thyroid hormone triiodothyronine (T3) during metamorphosis of the amphibian epidermis, we have investigated the developmental activation of the 63-kD keratin genes in the frog Xenopus laevis. These genes code for three closely related keratins that first appear in the larval epidermis and accumulate during metamorphosis to become the most abundant proteins in the adult epidermis. We report here that the 63-kD keratins and their mRNAs first appear at stages 48-52. The level of 63-kD keratin gene expression remains relatively low until stage 56 and then increases dramatically. Quantitative analysis of the concentration of 63-kD keratin mRNA demonstrates low levels until stage 55/56, followed by an increase greater than 300-fold from stage 55/56 to the adult. Each adult cell contains approximately 55,000 molecules of the 63-kD keratin mRNAs. T3 is not required for the initial activation of the 63-kD keratin genes, but high-level expression is absolutely dependent on T3. High-level expression is prevented by propylthiouracil, which inhibits thyroid hormone synthesis and can be induced precociously both in vivo and in vitro with exogenous T3 as early as stage 48, but not prior to that time. Thus, the full activation of the 63-kD keratin genes during development requires two regulatory steps, one independent and one dependent on T3.

Animals↗
PubMed1987

Nucleotide sequence of the streptolysin O (SLO) gene: structural homologies between SLO and other membrane-damaging, thiol-activated toxins.

The complete nucleotide sequence of a cloned streptolysin O (SLO) gene and the amino acid sequence of SLO, predicted from the DNA sequence, are reported. SLO contains a single cysteine residue located close to the C terminus of the molecule and shares extensive structural homologies with other thiol-activated toxins, which allow us to predict functionally important features.

Amino Acid Sequence↗
PubMed1987

Organizing color in dentistry.

Although esthetic dentistry techniques have grown more sophisticated, the fabrication and control of color in dentistry can be improved. An organized and precise system is necessary to combine artistic and scientific approaches. For this, a color order system, based on Munsell's notations and spectrophotometric research on the color space of natural teeth, would provide restorations of excellent color.

Audiovisual Aids↗
PubMed1987

Self-help and the patient/professional partnership.

The Surgeon General's Workshop on Self-Help and Public Health was convened to bring together professionals and lay people to develop recommendations and strategies related to how the Public Health Service might best address the goals of promoting a partnership between health care and self-help/mutual support systems for improved public health. The following four articles are adapted from presentations made at the workshop.

Breast Neoplasms↗
PubMed1987

Clinical trials of transfer factor in malignancy.

Results of clinical trials of transfer factor therapy in various malignancies have been variable. In non randomized trials, about 300 patients have been evaluated, and clinical benefit has been reported in about 1/3 of the evaluable patients. Results of randomized studies are similarly varied. In some randomized trials, clinical benefits of increased disease free survival and prolonged survival have been claimed. In other studies, transfer factor has been reported to be of no clinical benefit. In a few studies, results suggest patients receiving transfer factor do not do as well as those receiving placebo, although these are only trends, and do not reach the level of statistical significance. There are a number of variables in the design of transfer factor trials, and review of the studies performed to date does not permit a determination of which, if any, of these variables is related to the therapeutic outcome. A variety of tumor types have been evaluated, and it is not clear which, if any, tumors respond to transfer factor. Similarly, the state of disease and prior and concomitant therapy vary widely in these trials and the impact of these variables is unclear. The source and dose of transfer factor also varies. In some studies, attempts have been made to select donors who might have cellular immune reactivity to the tumor being treated, whereas in other studies normal donors have been used. The rationale for the use of normal donors in that the clinical benefit of transfer factor may be related to the non specific immunopotentiating effects of this agent rather than the specific transfer of cellular immunity. Finally, the methods of preparation of transfer factor vary and the products used in various studies cannot be compared by standard biologic or biochemical tests currently available. This review of the literature regarding the clinical effort of transfer factor in malignancy leads to the conclusion that transfer factor might not be an effective therapy of cancer. If it does have efficacy in certain malignancies, it is unlikely that it will alone have dramatic effects in substantial numbers of patients. Perhaps transfer factor may have a role in tumor therapy as an adjuvant to other forms of therapy and as surgery, irradiation, or chemotherapy. In order for the proper evaluation of transfer factor in reproducible comparative studies, it will be necessary to have a standarized reproducible product which can be assessed by appropriate quality control procedures.(ABSTRACT TRUNCATED AT 250 WORDS)

Breast Neoplasms↗
PubMed1987

Factors affecting monoclonal antibody production in culture.

Factors that affect production of monoclonal antibodies (McAb) by a murine cell line were investigated. The goal was to estimate the efficiency of large scale production in stirred reactors. It was found that in batch cultures most McAb was produced after the log growth phase; final yield was 100-200 micrograms/ml. Yields of McAb were increased to 290 micrograms/ml by feeding cells glucose and glutamine. Lactic acid, which was produced in culture as a result of glucose metabolism, had no toxic effect on cells, while another waste product, ammonium ion, was probably accumulated at toxic levels during late stages of cell growth. The hybridoma cell line was propagated in four different systems: fed-batch, semi-continuous, two stage and perfusion. These systems were compared to batch cultures for their effect on cell viability and antibody production. Daily addition of fresh medium (fed-batch propagation) increased antibody productivity from 15 (batch culture) to 27 mg/l of culture/day. In the semi-continuous culture productivity was raised to 34 mg/l/day. Further increase in productivity to a level of 62 mg/l/day was achieved by applying a second batch stage to the semi-continuous culture. A perfusion culturing method was the most effective for production of McAb. Average concentrations of 2.2 X 10(7) live cells/ml and 390 micrograms of antibody/ml corresponding to productivity of 660 mg/l/day were achieved. Serum concentration in the medium was reduced to 0.125% resulting in a specific activity of 0.4 mg of McAb per mg of protein in the cell-free culture broth.

Ammonia↗
PubMed1987

A geriatric neuropsychiatric inpatient unit.

Geriatric neuropsychiatry units have been developed in hospitals in various parts of the United States to provide an intensive diagnostic and treatment program for geriatric patients who have behavioral problems or the early signs of dementia. The Geriatric Neuropsychiatry Unit at the Boston City Hospital is described as a model unit. The process of patient selection and admissions criteria are outlined. Diagnostic interventions and the full evaluative process are then presented, followed by a summary of the therapeutic interventions. These interventions include pharmacologic, psychotherapeutic, behavioral, and milieu therapies. The communications process essential for effective multidisciplinary team function is also reviewed. Discharge planning procedures are presented, along with a summary of patient outcomes.

Aged↗
PubMed1986

Kinetics of monoclonal antibody production in low serum growth medium.

Factors affecting growth and monoclonal antibody production in vitro by a mouse-mouse hybridoma cell line have been investigated in a series of studies. The goal was to maximize antibody yields and demonstrate that antibodies can be produced efficiently on a large-scale in fermentors. This initial report describes (i) development of a radial immunodiffusion assay for accurate determination of antibody levels in culture, (ii) a culture medium formulation that allowed for reduction in the amount of fetal bovine serum required for good cell growth, and (iii) the kinetics of cell growth and monoclonal antibody production in low-serum media. The radial immunodiffusion assay, employing rabbit anti-mouse IgG antibodies in the immobile phase and the monoclonal antibody (an IgG2a to Rhizobium japonicum cells) as the antigen in the mobile phase, was more reproducible and reliable for determining antibody levels in culture broth than was an indirect enzyme-linked immunosorbent assay. Addition of 0.25% Primatone RL and 0.01% Pluronic F-68 to Dulbecco's modified Eagle medium allowed cells to adapt to growth in medium containing as little as 1% fetal bovine serum; without these additives, 5% serum was the lowest level attained. For the kinetic studies, cells were grown in the low-protein medium in 3 liter spinner flasks. Antibody production occurred during the growth phase, however, significant amounts were also produced during later phases when the cells had stopped growing. Final titers were 100-200 micrograms/ml. It was concluded that maintenance of cell viability is more important than growth rate in production of antibody. This conclusion, confirmed in other studies, has developed into the major underlying strategy employed in subsequent investigations to maximize antibody production in stirred reactors.

Animals↗
PubMed1986

Factors affecting cell growth and monoclonal antibody production in stirred reactors.

Environmental and cultural factors that could affect growth and cell viability of mouse-mouse hybridoma cells in culture were investigated. The aim was to determine conditions that could prolong viability and result in increased yields of monoclonal antibodies in stirred reactors. Factors studied included temperature, level of dissolved oxygen, nutrient depletion, and waste product accumulation. Growing cells at temperatures 3-9 degrees lower than optimum (37 degrees C) increased viability but monoclonal antibody production was lowered. A low level of dissolved oxygen (25% air saturation compared to 60% for optimum growth) prolonged cell viability and increased the monoclonal antibody yield by about 50%. Feeding cultures daily to maintain the glucose level above 1 mg/ml and at the same time feeding cells glutamine (150 micrograms/10(6) cells per day) maintained the level of viable cells at 1.7 X 10(6)/ml for at least 9 days and resulted in an antibody yield of 290 micrograms/ml, about a 70% increase over cultures fed either glucose or glutamine alone. Ammonium ion, added to cell populations at levels produced in cultures, stopped cell growth and decreased antibody production. Another waste product, lactic acid, had no toxic effect when added to media at levels found in cultures. These results agree with our suggestion that monoclonal antibody production is enhanced by maintaining cell viability over a prolonged period and provide a base for investigating modes of hybridoma cell propagation in fermentors.

Ammonia↗
PubMed1986

Prenatal diagnosis of the Beckwith-Wiedemann syndrome.

We report on the prenatal diagnosis of Beckwith-Wiedemann syndrome (BWS) in a pregnancy monitored because of a previously affected child. The proposita had classical stigmata of BWS including macroglossia, omphalocele, and typical ear creases. Chromosomes were 46,XX. Both parents and the extended maternal family were clinically normal. In a subsequent pregnancy by another father, the mother had serial ultrasound monitoring at 13.5, 18, and 19 weeks gestation which showed an enlarged abdominal circumference and a 2-cm omphalocele. At termination the female fetus weighed more than two times the expected weight, had striking hypertrophy of skeletal muscles, a protuberant abdomen, and a 2-cm omphalocele and characteristic facial appearance. Autopsy confirmed generalized organomegaly. This is the first report of the prenatal diagnosis of BWS prior to 20 weeks in an at-risk family. The recurrence in this family emphasizes the difficulty in providing accurate genetic recurrence risks in BWS and suggests that ultrasonographic prenatal diagnosis should be offered to families even when the case appears to be "sporadic."

Abortion, Induced↗
PubMed1986

Post-tonsillectomy hemorrhage: incidence, prevention and management.

Tonsillectomy (with or without adenoidectomy) continues to be a commonly performed operation in the United States. Over the years, the incidence of post-tonsillectomy hemorrhage (reported between 0% and 20%) has decreased, but continues to pose serious problems. We reviewed 1,445 tonsillectomies performed over a 2-year period to study the incidence of post-tonsillectomy hemorrhage. Thirty-eight of 1,445 children (2.62%) had postoperative bleeding. The incidence of primary hemorrhage (within 24 hours) was 0.14%. Delayed hemorrhage requiring operative intervention or observation in the hospital was 1.03% and 0.76%, respectively. Ten patients (0.69%) had delayed hemorrhage of a minor nature that had stopped by the time they reached the hospital; these children were treated with observation alone and did not require hospitalization or operative intervention. The proposed reasons for this low rate of post-tonsillectomy hemorrhage include complete preoperative coagulation screening, meticulous attention to surgical technique, use of suction-cautery to obtain hemostasis and, possibly, use of postoperative antibiotics. Management of hemorrhage is discussed with respect to observation, surgical intervention, and blood transfusion.

Adolescent↗
PubMed1986

Tetrahydrobiopterin administration to rhesus macaques. Its appearance in CSF and effect on neurotransmitter synthesis.

Tetrahydrobiopterin, the hydroxylase cofactor (BH4) was administered (i.v. 20 mg/kg) to Rhesus monkeys. Within 90 min of its administration CSF cofactor levels increased significantly above baseline levels. Peak CSF levels were attained at 90-180 min time period following cofactor injection and returned to baseline gradually over the next 15 hrs. The increased brain cofactor levels had no apparent effect on synthesis of dopamine, norepinephrine or serotonin as evidenced by a lack of change in the levels of the metabolites homovalillic acid, 3-methoxy-4-hydroxyphenyleneglycol, and 5-hydroxyindoleacetic acid. The present results using primates suggest no apparent effect of increased cofactor levels on monoamine biosynthesis. However, it remains to be explored whether monoamine synthesis could be affected by increased cofactor levels in the pathological situation.

Animals↗
PubMed1986

Hyperproduction of an intracellular heterologous protein in a sacUh mutant of Bacillus subtilis.

The sacR regulatory region which controls inducible expression of sacB, the gene for extracellular levansucrase, was isolated on a 500-bp fragment of Bacillus subtilis chromosomal DNA. The region was separated into two components: a 325-bp fragment which carries a constitutive promoter and a 175-bp fragment which carries a stem-loop structure presumably involved in the induction process. The constitutive sacR promoter was used to drive expression of the plasmid-borne xylE gene, coding for intracellular catechol 2,3-dioxygenase (C23O), with its Pseudomonas ribosome-binding site, in otherwise isogenic sacU-, sacU+ and sacUh mutant strains of B. subtilis. Mutations at the sacU locus have been previously shown to affect multiple cell functions, particularly production of extracellular enzymes. The presence of the sacUh mutation allowed for hyperproduction of C23O to levels exceeding 25% of total cellular protein. This represents a 50- to 100-fold enhancement over levels observed in sacU- and sacU+ host cells. A 5- to 10-fold improvement of C23O production in sacUh cells was observed when the subtilisin (aprA) promoter was used in place of sacR. In contrast, a bacteriophage T5 synthetic promoter was found to be independent of host strain for high-level synthesis of C23O. Hyperproduction of an intracellular protein in sacUh cells suggests that enhancement of exoenzyme production, previously observed in these mutants, occurs prior to the secretion event. Therefore, hyperproduction is most likely due to elevated transcription or translation of specific nucleotide sequences.

Bacillus subtilis↗
PubMed1986

Hemodynamic effects of intravenous cocaine on the pregnant ewe and fetus.

Cocaine is a potent vasoconstrictive agent that is currently the subject of widespread drug abuse. Because little is known of the physiologic responses to cocaine in pregnancy, the effects of intravenous cocaine on uterine blood flow and other maternal and fetal cardiovascular parameters were studied. Eight ewes in late pregnancy were equipped with electromagnetic flow probes around both uterine arteries and catheters were placed in the maternal and fetal inferior vena cavae and aortas. Bolus intravenous infusion of 0.5 and 1.0 mg/kg of maternal body weight achieved peak plasma cocaine levels similar to those observed in human subjects after abuse of the drug (mean level = 229 to 400 ng/ml, n = 8). After bolus infusion of 0.5 or 1.0 mg/kg of cocaine, mean maternal arterial pressure increased 32% and 37%, respectively (p less than 0.005). Fetal blood pressure rose 12.6% after a dosage of 0.5 mg/kg of cocaine. These cocaine infusions significantly decreased uterine blood flow by 36% and 42% for a duration of 15 minutes (p less than 0.005). Analysis of maternal catecholamine responses demonstrated a significant (210%) rise in plasma norepinephrine levels after cocaine infusion. These studies demonstrate that cocaine, when administered in doses that produce plasma levels observed in humans, significantly decreases uterine blood flow for a duration of greater than or equal to 15 minutes while inducing a hypertensive response in the pregnant ewe and fetus.

Animals↗