Search PubMedSearch

Biomedical subjects

M Decker

Publications and source records attributed to M Decker.

At least 19 recordsLinked to original sources

Antibody response to Bordetella pertussis antigens after immunization with American and Canadian whole-cell vaccines.

Because of apparent differences in the incidence and epidemiology of pertussis in the United States and Canada, we measured the antibody response to four Bordetella pertussis antigens and to a whole-bacteria preparation in children immunized with American and Canadian whole-cell pertussis vaccines. All infants received combined pertussis, tetanus, and diphtheria vaccines from one of two American manufacturers or a single Canadian manufacturer. The Canadian children received either oral poliomyelitis vaccine, inactivated poliomyelitis vaccine as a separate injection, or a product that combined inactivated poliomyelitis vaccine with diphtheria, tetanus, and pertussis components. The Canadian trivalent diphtheria, tetanus, and pertussis vaccine given with oral poliovirus vaccine induced lower anti-pertussis toxin antibody titers than did the American vaccines (p < or = to 0.05) but higher antifimbriae and anti-69-kilodalton outer-membrane protein (pertactin) antibody titers (p < or = to 0.02). Canadian children immunized with inactivated poliomyelitis vaccine either as a separate injection or as a combined diphtheria, tetanus, and pertussis vaccine had consistently lower pertussis antibody titers than did those who received oral poliomyelitis vaccine (p < or = 0.001). We conclude that there is a wide range of antibody responses to B. pertussis antigens after immunization with various whole-cell pertussis vaccines, and that these responses may be influenced by concurrent administration of other vaccines.

Antibodies, Bacterial

Structure/activity relationships in basic FGF.

Although the FGFs have been subject to extensive biological studies, only limited progress has been made so far in determining the critical elements of structure-activity relationships in the FGFs. Among the recognized structural elements with potential to affect the biological activity of FGFs are the cysteine residues, and the heparin- and receptor-binding domains. These features have been studied using a variety of experimental approaches, but the available data are inconclusive. For example, ambiguity regarding the presence of a disulfide structure in FGFs was not resolved until the availability of x-ray crystal structure data. Furthermore, the functionally important heparin- and receptor-binding domains have been poorly characterized, with some interpretations being controversial. In this report, we describe a novel fragment of basic FGF (bFGF) with high biological activity [Ser78,96-bFGF(70-153)]. This fragment was generated by pronase treatment of heparin-bound recombinant Glu3,5Ser78,96-bFGF mutant and is active in vitro at an ED50 of about 100 ng/ml. The structure of the fragment and the manner by which it was generated provide additional insight into important aspects of structure-activity relationships in FGFs. Specifically, we conclude that (a) the cysteines in our bFGF mutant do not form a disulfide bond, (b) the high-affinity heparin binding of bFGF critically depends on an intact 3-dimensional structure of the growth factor rather than on specific heparin-binding sequence domains, and (c) the bFGF sequence between residues 70 and 122 is important for high biological activity.

Binding Sites

Uveal melanoma: development of metastases after helium ion irradiation.

Forty-two (16%) of 261 patients with ocular melanoma who were treated with helium ions between January 1978 and November 1986 have developed metastatic disease. The time between start of helium ion treatment and recognition of metastatic disease ranged from 3 to 67 months (median, 27 months). The mean pretreatment tumor height in the patients with metastases was 7.7 mm. All 42 patients who developed metastatic disease have died. The median survival after diagnosis of metastatic disease was 5 months; the longest survival was 49 months. The most common site of metastasis was the liver (n = 34). Four (10%) of the 42 patients with metastases also had local recurrence of the tumor. Multivariate analysis identified three variables that predicted independently the development of metastases and lack of survival. These variables are anterior location of tumor (P = .027), tumor height greater than 5 mm (P = .02), and tumor diameter greater than 10 mm (P = .0075).

Actuarial Analysis

Isolation from bovine brain and structural characterization of HBNF, a heparin-binding neurotrophic factor.

A heparin-binding protein with neurotrophic activity for perinatal rat neurons, termed HBNF, was purified to homogeneity from bovine brain utilizing pH 4.5 extraction, ammonium sulfate precipitation, cation exchange and heparin-Sepharose affinity chromatographies, and reverse phase HPLC. In the presence of protease inhibitors during extraction, a protein with an apparent molecular weight of 18 kDa was obtained in a yield of approximately 0.5 mg/kg brain tissue. The amino acid sequence of the first 114 residues of HBNF was determined and found to highly homologous to the cDNA-derived amino acid sequence of human HBNF, a 136-residue protein. Bovine and human HBNFs have identical molecular weights as judged by SDS gel electrophoresis and very similar amino acid compositions. This and overall sequence conservation suggest that bovine HBNF is also a 136 amino acid protein with a calculated molecular weight of approximately 15.5 kDa. The apparent discrepancy between calculated and observed molecular weights of bovine HBNF (and of human HBNF of which the complete sequence is known) is most likely a result of the highly basic nature of HBNF. If protease inhibitors were omitted during tissue extraction, two additional proteins with lower apparent molecular weights and identical N-terminal sequences were isolated, with the smallest forms being the major product. Amino acid analysis showed that the smaller forms correspond to C-terminally truncated HBNFs with calculated molecular weights of 13.6 and 12.4 kDa, lacking approximately 14 and 22 residues. Comparison of the HBNF protein sequence with sequences stored in the Protein Identification Resource/Genbank databases reveals high homology to the translation product of the MK-1 gene, which is retinoic acid-inducible in embryonic carcinoma cells and developmentally expressed during gestation in mice.

Amino Acid Sequence

[Technical measuring procedures for 3-dimensional movement analysis of experimentally-induced fractures of the thoracolumbar spine and initial results].

Biomechanics and motion following fractures of the thoracolumbar spine have not yet been clarified. The motion acts in 6 degrees of freedom: three rotations and three translations parallel to the system of coordinates. The problem is to measure each rotation and each translation individually. This requires a method allowing precise three-dimensional evaluation of the motion that takes place in the genesis of a spine fracture. This technique should not influence the experiment, should give exact data over a wide range of measurement and, finally, should require as little equipment as possible. To fulfil these conditions we have developed a "double cube" model. Cadaver spine units from T11 to L3 were used. T11 was blocked with T12 and L2 with L3. These blocks were used to fix the spine in a testing machine so that a wedge-compression fracture could be produced in L1. Dorsal to each of the blocks one cube was mounted, the caudal one fixed while the cranial one could be moved by the machine. In the caudal cube a right-handed cartesian system of coordinates was defined, in which the vertebrate above would move and break. This technique can be used to describe either physiological or fracture experiments or, for example, to compare stability tests for different fixation devices. It is demonstrated that precise three-dimensional description of the biomechanics of vertebral fractures is possible with little and simple equipment. The cubes in this model are easily to integrate in the experiment.(ABSTRACT TRUNCATED AT 250 WORDS)

Biomechanical Phenomena

Long-term results of helium ion irradiation of uveal melanoma.

Between 1978 and 1988, 307 patients with uveal melanoma were irradiated using helium ions at Lawrence Berkeley Laboratory. The length of follow-up ranged from 1-115 months (median 42 months). The 5-year actuarial treatment results were: local control rate, 96.8%, determinate survival rate, 81%, freedom from distant metastases, 76%, eye retention rate, 83%, and risk of developing neovascular glaucoma, 36%. Long-term vision outcome was analyzed in 81 patients with a minimum follow-up of 5 years. Forty-seven percent of patients retained vision of 20/200 or better. The median change in vision was a loss of four lines on the standard eye chart. Thirty-eight percent of patients had visual acuity either improve or remain within two lines of their pretreatment vision. A multivariate analysis identified tumor size as the only independently significant risk factor affecting survival, development of neovascular glaucoma, or the risk of enucleation; no risk factor correlated with local recurrence. Tumor size, tumor-fovea distance, and pretreatment visual acuity were independently significant risk factors influencing vision outcome. These results confirm that helium ion irradiation is an effective treatment for uveal melanoma which combines high rates of local control, survival, and eye retention with a substantial likelihood of long-term vision preservation.

Adult

Ciliary body melanoma treated with helium particle irradiation.

Melanoma involving the ciliary body is a rare tumor which carries a poor prognosis when compared to all uveal melanoma. We have treated 54 patients with ciliary body melanoma using helium ions from 1978 to 1985. Because of the high rate of metastatic disease, the 5-year disease specific survival rate is only 59% despite a 5-year local control rate of 98%. The greatest diameter of the tumor was predictive of loss of vision and enucleation (p = .05, p = .04, respectively). Multivariate analysis showed that the greatest diameter of the tumor was the most important predictor of death from metastases. The incidence of neovascular glaucoma at 5 years is 43%. The 5-year actuarial rate of enucleation is 26%. Enucleation was done for pain and/or neovascular glaucoma. Univariate analysis showed treatment volume to be a statistically significant predictor for the development of neovascular glaucoma (p = .0017) and enucleation (p = .0078). Seventy percent of neovascular glaucoma occurred in patients with treatment volume greater than 5.5 cc. Seventy-four percent occurred in patients with an initial ultrasound height greater than 9.2 mm. Using this information, patients at high risk for neovascular glaucoma could be considered for prophylactic treatment with panretinal photocoagulation.

Adult

Seasonal characteristics of and age at menarche.

Data from approximately 600 U.S. women were analyzed for seasonality in menarche. Data were converted to the ratio of observed (O) to expected (E) cases, based on an equal distribution of events over the year, per considered time span of the year. The greatest O/E ratio in menarche (1.55) occurred during January, followed by August (1.43) and July (1.24). The lowest O/E ratio in menarche occurred in February and May (0.68). Seasonal patterns in menarche were detected for the separate cohorts of women born during the 1940s, 1950s, and 1960s, with a shift from a December-January peak in menarche for those born in the 1940s and 1950s to an August-September peak for those born in the 1960s. Girls who were younger (8-14 yrs) at menarche exhibited a seasonal difference in the peak number of menarches by about 6 months in comparison to the pattern for girls who were older (15-17 yrs). Girls who experienced menarche during August-October were statistically significantly younger (p less than 0.05) than those born during the other three seasons. Season of birth was not statistically significantly associated with season of menarche. Overall, no 12-month pattern was substantiated by cosinor analysis in the month of menarche. However, a 6-month rhythm was detected in menarche for women born between 1940 and 1960 (p = 0.004, A = 29% M, phi = January and July).

Adolescent

Seasonal characteristics of and age at menarche.

Several patterns in menarche are evident over time and across populations which vary by ethnicity, socioeconomic status and altitude of residence: peak occurrence of menarche in January and August with a possible minor peak in April; troughs in the occurrence of menarche to either side of the peak months; and secular trends in season and age patterns of menarche. Contradictory patterns in season of menarche with respect to age at menarche and season of menarche with respect to season of birth are still unresolved. Further research is yet required to evaluate the role of the variety of endogenous and exogenous variables and their interactions on menarche in order to more fully develop an appropriate understanding of the chronobiology of developmental and reproductive phenomena in women and their dependence upon environmental quality and temporal cues.

Adolescent

Hyaluronic acid-stimulating activity in sera from the bovine fetus and from breast cancer patients.

The sine qua non of malignancy is the ability of tumor cells to migrate and invade surrounding tissue. There are many substances that have been described that enhance cell motility and hyaluronic acid is prominent among these. Hyaluronic acid is a high molecular weight alternating disaccharide polymer found in abundance in extracellular matrices whenever rapid cell proliferation or tissue regeneration and repair occur. It creates a permissive environment for cell motility during embryogenesis, and high levels of hyaluronic acid also correlate with increased tumor cell invasion and aggressiveness. Little is known about the regulation of hyaluronic acid production, either in normal tissue or in malignancy. In this study, we characterize a hyaluronic acid-stimulating activity in fetal calf serum and describe a similar activity in the sera of breast cancer patients. The stimulating activity was measured by placing aliquots of test substance on fibrosarcoma cells. These indicator cells, which synthesize copious quantities of hyaluronic acid, respond to stimulation in a time- and dose-dependent fashion. The fetal calf serum hyaluronic acid-stimulating activity is maximum early in gestation and then falls rapidly to essentially no activity at term. This activity was partially purified from 120-day fetal calf serum by concanavalin A-Sepharose affinity and ion exchange chromatography and is accounted for by a glycoprotein with a molecular weight of 150,000 on gel filtration under native conditions. The sera of breast cancer patients with measurable burden of disease also contained hyaluronic acid-stimulating activity, which was not present in normal serum donors or in breast cancer patients without evidence of disease. The production of this stimulating activity may contribute to the development of the malignant phenotype by inducing hyaluronic acid-rich microenvironments that are permissive to tumor cell invasion and metastases.

Animals

Charged particle radiotherapy for lesions encircling the brain stem or spinal cord.

Since 1981, a specialized technique has been under development at the University of California Lawrence Berkeley Laboratory for charged particle irradiation of tumors partially or completely encircling the brain stem or spinal cord. By dividing the target volume into two or more portions and using a combination of beams, a reasonably homogeneous irradiation of the target volume can be obtained which protects critical CNS structures from over-irradiation. This technique requires knowledge of the physical and biological effects of charged particles, precise, reproducible patient immobilization, careful treatment planning based upon Metrizamide contrast CT and/or MRI scanning, compensation for tissue inhomogeneities, and accurate, verifiable radiation delivery. Uncertainties in the dose distribution must be taken into account when prescribing treatment. We have used this technique in 47 patients with a variety of tumors abutting the brain stem and spinal cord, including chordoma, chondrosarcoma, meningioma, osteosarcoma and metastatic tumors. The results have shown a significant local control rate (62%) and the incidence of serious complications has been acceptable (13%). The median follow-up is 20 months with a range of 6-90 months. We conclude that charged particles can be safely and effectively used to irradiate lesions encircling the brain stem or spinal cord to doses higher than can be achieved with low-LET irradiation.

Brain Neoplasms

Studies in fetal wound healing: I. A factor in fetal serum that stimulates deposition of hyaluronic acid.

Fetal wound healing without scar formations, fibrosis, or contracture might be accompanied by major differences in the wound extracellular matrix. The matrix of fetal wounds is rich in hyaluronic acid, a glycosaminoglycan found in high concentrations whenever there is tissue proliferation, regeneration, and repair. Although hyaluronic acid is a critical molecule for both embryonic development and wound healing, no factor has yet been identified that modulates hyaluronic acid in a consistent manner. We describe here a substance present in fetal sheep serum that stimulates hyaluronic acid synthesis by cultured fibroblasts. This glycoprotein factor appears to be ubiquitous, present in fetal sheep and bovine serum, reaching a peak in each at 40% of the way through gestation. This factor is also present in amniotic fluid. It might control hyaluronic acid deposition. In turn, hyaluronic acid, by creating an extracellular environment permissive for cell motility and proliferation, might be critical for fetal development. We suggest that the same sequence of events underlie the unique properties observed in fetal wound healing.

Animals

Circadian rhythms in hot flashes in natural and surgically-induced menopause.

The aim of this study was to investigate circadian and ultradian variations in menopausal hot flash. The number of hot flashes per 2-hr period was collected from 25 diurnally-active, perimenopausal women for 1 week in January or February of each year for 3 consecutive years. Fourteen women were experiencing natural menopause (NM) (mean age 51.9 years) and 11 were experiencing surgically-induced menopause (SIM) (mean age 52.0 years). The difference in the number of hot flashes between the two types of menopause at each clock time was not statistically significant; neither was the mean number of hot flashes per 24 hr different between the two groups (Student's t-test). Data when normalized for each woman and placed end-to-end revealed by cosinor analysis circadian rhythmicity in the SIM group (P = 0.02) but not in the NM group. A 12-hr periodicity was detected in both groups (P less than 0.001 for both). An 8-hr rhythm was detected only for the NM group (P = 0.04). Both groups combined exhibited statistically significant rhythmicities with periods of 24 hr (P = 0.003), 12 hr (P less than 0.001) and 8 hr (P = 0.005). Regardless of the type of menopause, the women could be separated into two groups based on the temporal pattern of hot flashes during the day. One group was defined by the occurrence of peak frequency of flashes during the morning (0400-0959), while the second group was defined by the occurrence of the peak in the evening (1600-2159).(ABSTRACT TRUNCATED AT 250 WORDS)

Activity Cycles

Lung cancer mortality among women employed in high-risk industries and occupations in Harris County, Texas, 1977-1980.

Lung cancer is rapidly becoming the leading cause of cancer mortality among women. Interviews conducted with 259 women with lung cancer and 278 women without lung cancer or with their next-of-kin in Harris County, Texas from July 1, 1977 to June 30, 1980 revealed that 12 (4.6%) of the women with lung cancer had never smoked cigarettes. The odds ratio (OR) for current smoking was 15.7. Odds ratios for smoking for living women (OR = 17.5) were higher than for those who were deceased (OR = 12.6). Lifetime occupational histories were classified a priori into high- and low-risk categories. Data were stratified according to employment in a high-risk industry or occupation, a high-risk industry, a high-risk occupation, or both a high-risk industry and occupation. Although not statistically significant, odds ratios for employment in high-risk categories support earlier estimates that attributed 5% of lung cancer mortality in women to employment in hazardous occupations. Employment of a husband or household member in selected industries and occupations yielded significantly increased odds ratios. More cases (15.9%) than controls (6.9%) reported a family history of lung cancer (OR = 2.4). No significant increase in smoking-adjusted odds ratios was found for the use of hair spray, hand-held dryers, or alcohol, or for having lived with a household member who smoked cigarettes.

Adenocarcinoma