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J R Harris

Publications and source records attributed to J R Harris.

At least 73 records · Page 4Linked to original sources
PubMed1999

Keyhole limpet hemocyanin type 2 (KLH2): detection and immunolocalization of a labile functional unit h.

Keyhole limpet hemocyanin (KLH) is a mixture of two hemocyanin isoforms, termed KLH1 and KLH2. Within KLH1 eight oxygen-binding functional units (FUs), 1-a to 1-h, have been identified, in contrast to KLH2, which was previously thought to be organized in seven FUs (2-a to 2-g). By limited proteolysis of KLH2 subunits, isolation of the polypeptide fragments, and N-terminal sequencing, we have now identified an eighth FU of type h, with a molecular mass of 43 kDa. This is unusually small for a FU h from a gastropodan hemocyanin. It is also shown that KLH2 didecamers can be split into a stable and homogeneous population of decamers by dialysis against 50 mM Tris/HCl, pH 7.5, in the absence of divalent cations. Electron microscopic immunolocalization using a specific monoclonal antibody reveals that FU KLH2-h is located at the collar of the decamer.

Amino Acid Sequence↗
PubMed1999

Factors associated with regional nodal failure in patients with early stage breast cancer with 0-3 positive axillary nodes following tangential irradiation alone.

PURPOSE: Recent randomized trials have suggested that improved local-regional control after radiation therapy significantly increases survival for breast cancer patients with positive axillary nodes treated with adjuvant systemic therapy (1, 2). It has been our policy to use a third radiation field only in patients with 4 or more positive nodes. The purpose of this study was to assess whether there are any clinical or pathologic factors associated with an increased risk of regional nodal failure (RNF) in patients with 0-3 positive nodes treated with tangential radiotherapy (RT) alone with or without systemic therapy. METHODS AND MATERIALS: We retrospectively analyzed the incidence of RNF for 691 patients with clinical Stage I or II invasive breast cancer treated with complete gross excision of the primary tumor and tangential RT alone between 1978-87; 12% also received systemic therapy. All had 0-3 positive nodes on axillary dissection that had histologic examination of > or =6 nodes, and all had potential 8-year follow-up. The median number of axillary nodes removed was 11 (range 6-36). RNF was defined as any recurrence in ipsilateral axillary, internal mammary, supraclavicular, or infraclavicular nodes in the absence of recurrence in the breast, with or without simultaneous distant metastasis. Crude rates for first sites of failure within the first 8 years after treatment were calculated. A polychotomous logistic regression was used to identify factors prognostic for RNF and other sites of first failure. RESULTS: Within 8 years, RNF was the first site of failure for 27 patients for a crude 8-year rate of 3.9%. Isolated axillary failure occurred in 8 patients (1.2%). Isolated supraclavicular and/or infraclavicular failure occurred in 5 (1.3%) and 3 (0.4%) patients, respectively. Isolated internal mammary node failure occurred in 2 patients (0.3%). A polychotomous logistic regression model of first site of failure (local failure, regional nodal, distant/ opposite breast, dead without recurrence, no evidence of disease) within 8 years found age <50 years, moderate or marked necrosis, size greater than 1 cm, and presence of an extensive intraductal component (EIC) to be significantly correlated with site of first failure, but only the last two were associated with a significantly larger relative risk of RNF versus being no evidence of disease at 8 years. The incidence of RNF was 0.7% for patients with tumors < or =1 cm compared to 5.7% among patients with larger tumors. Among patients with EIC-positive tumors the incidence of RNF was 7.6% compared to 3.1% among those whose tumors were EIC-negative. CONCLUSIONS: Although the incidence of RNF has been shown to be somewhat higher in patients with tumors measuring greater than 1 cm and those with an EIC, RNF is uncommon among all subsets of patients with negative or 1-3 positive lymph nodes treated with conservative surgery, axillary dissection, and only tangential RT fields. Therefore, giving only tangential RT (without a separate nodal field) appears generally acceptable for patients with 0-3 positive nodes.

Adult↗
PubMed1999

Concurrent CMF and radiation therapy for early stage breast cancer: results of a pilot study.

PURPOSE: The optimal sequencing of chemotherapy (CT) and radiotherapy (RT) for patients with early-stage breast cancer treated with breast-conserving therapy is unresolved. Given the concerns arising from delaying either CT or RT, we conducted a pilot study of a concurrent CT-RT regimen in the hope that this would reduce side effects without decreasing efficacy. METHODS AND MATERIALS: From 1992-1994, 112 patients with 0-3 positive nodes received 6 monthly cycles of classic oral chemotherapy with cyclophosphamide, methotrexate, and 5-fluorouracil (5-FU) (CMF). On day 15 of cycle 1, patients started tangential field RT (39.6 Gy in 22 fractions), followed by a 16 Gy boost in 8 fractions. Median follow-up time for surviving patients was 53 months. RESULTS: Moist desquamation developed during or shortly after RT in 50% of patients, but only 5 patients required treatment breaks. Grade 4 neutropenia during RT occurred in 16 patients, but only 1 required hospitalization. One patient developed Grade 2 radiation pneumonitis. Ninety-three percent of patients received at least 85% of prescribed drug doses. Cosmetic scores of 51 evaluable patients approximately 2 years after the end of chemotherapy were 47% excellent, 43% good, and 10% fair. We have observed 4 local failures and 20 distant failures. CONCLUSIONS: This concurrent CT-RT scheme had acceptable toxicity and outcome. Further comparison of this approach allowing prompt initiation of both CT and RT to alternative sequences is warranted.

Adult↗
PubMed1999

[What can twin research reveal about the causes of diseases?].

The purpose of this paper is to describe the place of twin studies in etiological research on somatic diseases, using asthma as an example. Twin studies provide answers to the relative importance of genes and environment in the development of disease, but have been criticised for systematic biases especially linked to unusual conditions in twin pregnancies. For asthma, classical twin studies show that genes explain the largest part of the interindividual variability, and that common family environment does not explain similarity in asthma in siblings. The assumptions underlying classical twin studies are discussed. A few other twin designs are mentioned, and we conclude that twin studies still play an important role in understanding causes of somatic diseases.

Asthma↗
PubMed1999

Treatment-related toxicity from a randomized trial of the sequencing of doxorubicin and radiation therapy in patients treated for early stage breast cancer.

PURPOSE: There is concern that breast cancer patients treated with left-sided radiation therapy (XRT) and doxorubicin (DOX) may have an increased risk of cardiac toxicity. In addition, the effect of different sequencing of XRT and chemotherapy (CT) on the likelihood of cardiotoxicity, as well as cellulitis, arm edema, or brachial plexopathy, is not well understood. We reviewed the records of patients treated on a randomized trial testing the sequencing of CT and XRT to determine if there was an increase in cardiac events or other complications in patients treated with a total dose of DOX of 180 mg/m2 and XRT, comparing patients with treatment to the left breast and the right breast, and comparing patients treated with initial CT and initial RT. MATERIALS AND METHODS: From June 1984 to December 1992, 244 patients with clinical stage I or II breast cancer were randomized following conservative surgery to receive CT (4 cycles of CAMFP at 3 week intervals) either before or after XRT (45 Gy to the entire breast, followed by a boost of 16 Gy; nodal radiation therapy was optional). Two hundred thirty-one patients were evaluable for the development of cardiac toxicity. The median age at diagnosis was 45 years (range, 20-68). CT doses were: doxorubicin, 45 mg/m2 IV bolus, d 3; methotrexate, 200 mg/m2 IV, d 1 and 15; 5-fluorouracil, 500 mg/m2 IV, d 1; cyclophosphamide, 500 mg/m2 IV, d 1; prednisone 40 mg p.o., d 1-5. A cardiac event was defined as a myocardial infarction or clinical evidence of congestive heart failure. Median follow-up time was 53 months. RESULTS: No cardiac events were observed for patients with either left- or right-sided breast cancer. The sequencing of CT and XRT had no significant effect on the risk of cardiac toxicity, cellulitis, arm edema or brachial plexopathy. CONCLUSIONS: We observed no evidence of an increased risk of cardiac toxicity from the addition of left breast tangential irradiation to DOX at a total dose of 180 mg/m2. Additional follow-up is needed to exclude possible late events. In addition, the sequencing of CT and XRT does not appear to affect the risk of cellulitis, arm edema, or brachial plexopathy.

Adult↗
PubMed1999

Anticonvulsant actions of LY 367385 ((+)-2-methyl-4-carboxyphenylglycine) and AIDA ((RS)-1-aminoindan-1,5-dicarboxylic acid).

We have studied the effects in three rodent models of generalised convulsive or absence epilepsy of two antagonists of group I metabotropic glutamate receptors that are selective for the mGlu1 receptor. LY 367385 ((+)-2-methyl-4-carboxyphenylglycine) and AIDA ((RS)-1-aminoindan-1,5-dicarboxylic acid) have been administered intracerebroventricularly (i.c.v.) to DBA/2 mice and lethargic mice (lh/lh), and focally into the inferior colliculus of genetically epilepsy prone rats (GEPR). In DBA/2 mice both compounds produce a rapid, transient suppression of sound-induced clonic seizures (LY 367385: ED50 = 12 nmol, i.c.v., 5 min; AIDA: ED50 = 79 nmol, i.c.v., 15 min). In lethargic mice both compounds significantly reduce the incidence of spontaneous spike and wave discharges on the electroencephalogram, from <30 to >150 min after the administration of AIDA, 500 nmol, i.c.v., and from 30 to >150 min after the administration of LY 367385, 250 nmol, i.c.v. LY 367385, 50 nmol, suppresses spontaneous spike and wave discharges from 30 to 60 min. In genetically epilepsy prone rats both compounds reduce sound-induced clonic seizures. LY 367385, 160 nmol bilaterally, fully suppresses clonic seizures after 2-4 h. AIDA is fully effective 30 min after 100 nmol bilaterally. It is concluded that antagonists of mGlu1 receptors are potential anticonvulsant agents and that activation of mGlu1 receptors probably contributes to a variety of epileptic syndromes.

Acoustic Stimulation↗
PubMed1999

Predictors of local recurrence following excision alone for ductal carcinoma in situ.

BACKGROUND: The treatment of ductal carcinoma in situ (DCIS) remains controversial, particularly in regard to the selection of patients who may be appropriately treated with wide excision alone. To help identify such patients, the authors assessed prognostic factors for local recurrence in patients with DCIS treated with excision alone. METHODS: The study population consisted of 59 patients diagnosed with DCIS between 1985 and 1990. All had been treated with excision alone, had their histologic slides available for re-review by a study pathologist, and had negative margins of excision on review. The median age at diagnosis was 54 years, and the median follow-up time was 95.5 months. Ninety-six percent presented with mammographic findings only; all patients had a reexcision. The size of the DCIS was assessed by the total number of low-power fields (LPF) in which DCIS was present (median LPF = 5). RESULTS: Ten patients experienced a local recurrence (LR) at 5-132 months (median, 37 months) after excision. The actuarial 5-year LR rate was 10%. Four of the recurrences were invasive carcinomas, and 6 were DCIS. No patients have developed metastatic disease or have died of disease. Lesion size >5 LPF was the only significant prognostic factor for local recurrence on univariate analysis (3% vs. 17% for < or = 5 vs. > or = 5 LPF, P = 0.02) and in proportional hazards models. Although patients with nuclear Grade 3 lesions had a higher LR rate than those with nuclear Grade 1 and 2 lesions (18% vs. 6% and 5%, respectively) and patients with close margins (< or = 1 mm) had a higher LR rate than patients with negative margins (>1 mm) (25% vs. 8%), these differences did not reach statistical significance. Among the 19 cases with margins negative by more than 1 mm, lesion size < or = 5 LPF, and nuclear Grade 1 or 2, there were no LRs; by contrast, the remaining 40 patients had a 5-year actuarial LR rate of 15% (P = 0.08). CONCLUSIONS: Lesion size was the only statistically significant prognostic factor for local recurrence in this series of patients with DCIS treated with excision alone. Other factors, such as margin status and nuclear grade, may also be useful in the identification of patients with DCIS who can be managed with excision alone. However, the most reliable and reproducible method of assessing these factors and the best way to combine them have not been determined.

Adult↗
PubMed1999

Ultrastructure, fractionation and biochemical analysis of Cryptosporidium parvum sporozoites.

Sporozoites of the apicomplexan parasite Cryptosporidium parvum were subjected to cell disruption and subcellular fractionation using a sucrose density step gradient. With this procedure, highly enriched preparations of the parasite membrane, the micronemes, dense granules and amylopectin granules were produced. No separate fraction containing rhoptries was obtained, however this organelle was found in defined fractions of the gradient, still associated with the apical tip of the sporozoites. Using negative staining, the internal structure of the micronemes was revealed by transmission electron microscopy. Micronemes and dense granules showed characteristic protein compositions by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The micronemes contained three major proteins of approximately 30, 120 and 200 kDa and the dense granules contain five major proteins in the 120-180 kDa range.

Animals↗
PubMed1999

An ounce of prevention ... what are the returns? Second edition, 1999.

CONTEXT: Because human and financial resources are limited, health efforts must focus on prevention strategies that yield the most benefit for the investment. Many current strategies identified in the literature offer opportunities to promote health at a reasonable cost. OBJECTIVE: To present a literature-based review of evidence demonstrating that prevention can be an effective and wise use of resources through CDC's An Ounce of Prevention ... What Are the Returns? Second Edition. DESIGN: Systematic review of cost-effectiveness literature for a selected group of prevention strategies. SETTING: Prevention strategies relevant to the U.S. population. RESULTS: Data indicate that the health conditions considered can be addressed through prevention strategies that are either cost effective or cost saving. CONCLUSIONS: An Ounce of Prevention ... What Are the Returns? Second Edition can be used to conveniently access information on prevention strategies, the diseases and injuries they address, and their cost effectiveness. It also complements other comprehensive prevention guides. However, limitations of the available cost-effectiveness studies indicate that standardized procedures should be followed for studies of all recommended prevention strategies. Researchers must standardize review procedures to improve both the quality and comparability of studies.

Adolescent↗
PubMed1999

Keyhole limpet hemocyanin (KLH): a biomedical review.

In this review we present a broad survey of fundamental scientific and medically applied studies on keyhole limpet hemocyanin (KLH). Commencing with the biochemistry of KLH, information on the biosynthesis and biological role of this copper-containing respiratory protein in the marine gastropod Megathura crenulata is provided. The established methods for the purification of the two isoforms of KLH (KLH1 and KLH2) are then covered, followed by detailed accounts of the molecular mass determination, functional unit (FU) structure, carbohydrate content, immunological analysis and recent aspects of the molecular genetics of KLH. The transmission electron microscope (TEM) has contributed significantly to the understanding of KLH structure, primarily from negatively stained images. We give a brief account of TEM studies on the native KLH oligomers, the experimental manipulation of the oligomeric states, together with immunolabelling data and studies on subunit reassociation. The field of cellular immunology has provided much relevant biomedical information on KLH and has led to the expansion of use of KLH in experimental immunology and clinically as an immunotherapeutic agent; this area is presented in some detail. The major clinical use of KLH is specifically for the treatment of bladder carcinoma, with efficacy probably due to a cross-reacting carbohydrate epitope. KLH also has considerable possibilities for the treatment of other carcinomas, in particular the epithelially derived adenocarciomas, when used as a carrier for carcinoma ganglioside and mucin-like epitopes. The widespread use of KLH as a hapten carrier and generalised vaccine component represent other major on-going aspects of KLH research, together with its use for the diagnosis of Schistosomiasis, drug assay and the treatment of drug addiction. Immune competence testing, assessment of stress and the understanding of inflammatory conditions are other areas where KLH is also making a useful contribution to medical research.

Adjuvants, Immunologic↗
PubMed1999

Half of the variation in susceptibility to mortality is genetic: findings from Swedish twin survival data.

Molecular epidemiological studies confirm tremendous variability in genetic and environmental susceptibility to disease and death for humans. This variability as well as the roles of genetic and environmental factors in susceptibility to death can be estimated in the analysis of survival data on related individuals (e.g., twins). In this paper, correlated gamma-frailty models are applied to survival data on Swedish twins to estimate genetic parameters in six models of susceptibility. It is shown that the frailty model with additive genetic and nonshared environmental components fits the data best. The estimate of narrow-sense heritability in gamma frailty is about 50%. The results of genetic analysis confirm our earlier findings from the studies of Danish twins that about 50% of individual susceptibility approximated by gamma-distributed frailty is heritable.

Cohort Studies↗
PubMed1999

Controlled cleavage of KLH1 and KLH2 by the V8 protease from Staphylococcus aureus reassociation, electrophoretic and transmission electron microscopy study of peptide fragments.

The reassociation behaviour of protease V8-cleaved peptides from KLH1 and KLH2, the two hemocyanin isoforms from the giant keyhole limpet Megathura crenulata, has been studied by transmission electron microscopy of negatively stained specimens and SDS/PAGE. Reassociation of the complete mixture of protease cleavage products and of combinations of peptide fragments purified by HPLC was performed in the presence of 100 mm CaCl2 and 100 mm MgCl2 at pH 7.4, over a period of 1 to 4 weeks. The V8 protease splits KLH1 into peptide fragments containing the functional units abc, def, defg, defgh, g and h. This mixture of peptide fragments reassociated to form helical tubular polymers, with a diameter of approximately 25 nm. The single functional units g and h were not incorporated into the polymer. An essentially identical polymer was formed from the re-mixed HPLC-purified fragments abc, def and defg alone. As with uncleaved subunit, the tubular polymer of V8-cleaved KLH1 forms bundles. The combination of peptides def and defg led to the formation of short arc-like filamentous structures, which aggregated but showed little tendency to associate into larger polymers. The KLH1 peptide fragments abc and def alone, did not reassociate and in combination their potential to form polymers was very low. With KLH2, the V8 protease generated peptide fragments containing the functional units abc, defg, defgh and h, which in combination slowly reassociated to form a tubular polymer significantly different to that obtained from the KLH1 V8 fragments. The three-functional unit fragment abc from KLH2 showed no tendency to polymerize and the combination of peptides defg + defgh generated only disordered aggregates, with some indication of malformed tubules. The combination of biochemical and electron microscopical methods enabled the characterization of these polymers with respect to peptide composition and higher order structure.

Electrophoresis, Polyacrylamide Gel↗
PubMed1999

Genetic effects on weight change and food intake in Swedish adult twins.

BACKGROUND: Obesity is influenced by genetic and environmental factors. Additionally, synergistic effects of genes and environments may be important in the development of obesity. OBJECTIVE: The aim of this study was to test for genetic effects on food consumption frequency, food preferences, and their interaction with subsequent weight gain. DESIGN: Complete data on the frequencies of consumption of 11 foods typical of the Swedish diet were available for 98 monozygotic and 176 dizygotic twin pairs aged 25-59 y who are part of the Swedish Twin Registry. The data were collected in 1973 as part of a questionnaire study. Body mass index was measured in 1973 and again in 1984. RESULTS: There was some evidence that genetic effects influenced the frequency of intake of some foods. Similarity among monozygotic twins exceeded that among dizygotic twins for intake of flour and grain products and fruit in men and women, intake of milk in men, and intake of vegetables and rice in women, suggesting that genes influence preferences for these foods. Analyses conducted for twins reared together and apart also suggested greater monozygotic than dizygotic correlations, but cross-twin, cross-trait correlations were all insignificant, suggesting that the genes that affect consumption frequencies are not responsible for mediating the relation between the frequency of intake and weight change. CONCLUSIONS: Genetic effects and the frequency of intake are independently related to change in body mass index. However, there was no suggestion of differential genetic effects on weight gain that were dependent on the consumption frequency of the foods studied.

Adult↗
PubMed1999

Neuroprotective actions of novel and potent ligands of group I and group II metabotropic glutamate receptors.

The role of group I metabotropic glutamate (mGlu) receptors in neurodegeneration is controversial because of the contradictory effects of mGlu1/5 agonists in in vitro models of neuronal cell death. In this study, novel and selective antagonists of mGlu1 and mGlu5: LY367385 and LY367366 were found to show consistent neuroprotective effects against N-methyl-D-aspartate (NMDA)-induced excitotoxicity in vitro and in vivo. Furthermore, intraventricular administration of LY367385 reduced hippocampal cell death in gerbils subjected to transient global ischemia. Previous studies have also shown that activation of group II mGlu receptors may contribute to neuroprotective mechanisms in vitro and in vivo. Three potent group II mGlu agonists--LY354740, LY379268 and LY389795--were found to attenuate both NMDA excitotoxicity and staurosporine-induced neuronal cell death. LY354740 and LY379268 were protective against transient global ischemia in gerbils when dosed intraperitoneally. These results support the view that antagonists of mGlu1 and mGlu5 and agonists of group II mGlu receptors may be useful agents in the therapeutic treatment of neurodegenerative disease.

Animals↗