Preparation of a genomic cosmid library.
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Animals↗
Biomedical subjects
M McCormick
Publications and source records attributed to M McCormick.
Sib selection.
Isolation of a particular clone from a library by sib selection is based on fractionating the library and choosing a positive subfraction which is consequently enriched for the clone of interest. The goal is to repeat this cycle until the enrichment process results in purification. As discussed in this chapter, particular patterns of fractionating are more efficient than others depending on the relative abundance of the clone, and the size of the original library. Importantly, sib selection is an isolation process that can be used in conjunction with any assay system. In particular, it may be used to isolate a gene from a library where there is an assay for the gene product, but no selection or sequence information available.
Animals↗
Factors predicting response of end stage squamous cell carcinoma of the head and neck to cisplatinum.
Cisplatinum significantly prolongs survival in end stage head and neck cancer but only 30-40% of patients respond. Many receive chemotherapy with little or no benefit and it would obviously be advantageous to determine in advance those patients likely to benefit. In 2 phase III trials of chemotherapy in end stage disease, 129 patients have been treated with cisplatinum, either alone or in 2-drug combination with bleomycin, methotrexate or 5-fluorouracil. Factors analysed in the entire group were age, sex, site, previous treatment, performance status and the use of cisplatinum in combination. A high albumen and oro- or nasopharyngeal site were significantly favourable, while a hypopharyngeal, middle ear, skin or paranasal site were all significantly unfavourable. In the separate analysis of the subgroup with recurrent disease, site of recurrence and time to recurrence were analysed in addition to the factors named above. Although similar trends to those in the entire group were observed none reached significant levels. In the subgroup with advanced previously untreated disease, histological grade was analysed in addition to the above factors. Good performance status emerged as significantly favourable. The emerging trends provide some insight regarding outcome but are not sufficiently clearcut to allow a decision to be made on who should and who should not be treated.
Antineoplastic Combined Chemotherapy Protocols↗
[Cisplatin and bleomycin in the treatment of advanced or recurrent squamous cell carcinoma of the head and neck. A randomized facultative Phase III controlled study].
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Bleomycin↗
The 5'-flanking sequences of human globin genes contribute to tissue specific expression.
The specificity of expression of the isolated 5'-flanking sequences of the human beta- and epsilon-globin genes was examined in the K562 human erythroleukemia cell line, the murine erythroleukemia (MEL) cell, and in nonerythroid cell lines CV-1, HeLa-S3, and WI-38. Globin flanking sequences were active only in the erythroid K562 and MEL cell lines. Furthermore, the upstream sequence of the adult, beta-globin gene was active in MEL cells which express adult globin and not in K562 cells which express embryonic and fetal globins suggesting that tissue specificity resides in these upstream sequences. No expression was observed in K562 cells which have an embryonic-fetal hemoglobin phenotype.
Acetyltransferases↗
Reconstitution of an operon from overlapping fragments: use of the lambda SV2 integrative cloning system.
We have used the lambda SV2 system [Howard and Gottesman. In Gluzman (Ed.), Eukaryotic Viral Vectors. Cold Spring Harbor Laboratory, Cold Spring Harbor, NY, 1982, pp. 211-216; in Inouye, M. (Ed.) Experimental Manipulations of Gene Expression. Academic Press, New York, 1983, pp. 137-153] to reconstitute the Salmonella typhimurium his operon from overlapping fragments. lambda SV2 can be propagated as an autonomously replicating plasmid or as a prophage integrated in the Escherichia coli chromosome at the lambda attachment site; our reconstitution was accomplished in the integrated state. We first inserted a portion of the his operon into lambda SV2 and integrated the resulting plasmid by site-specific recombination into the E. coli chromosome. This was achieved by brief induction of a resident prophage. The lysogen was then transformed with DNA from a lambda SV2 clone carrying the remainder of the his operon on an overlapping DNA fragment. The second plasmid was forced to integrate into the first by homologous recombination. When this recombination occurs at the his overlap, a lysogen carrying two lambda SV2 prophages is produced. One prophage carries the entire his operon and the other carries the his overlap region. The latter is removed by site-specific recombination, permitting further contiguous sequences to be sequentially added to the remaining prophage. This method should be applicable for the reconstitution and maintenance of large genes or gene clusters in the E. coli genome.
Alleles↗
Hürthle cell tumors: a twenty-five-year experience.
During a 25-year period (1959 through 1983), 54 patients with Hürthle cell tumors were treated and monitored at the University of Chicago Medical Center. Thirty percent were men and 70% were women; mean age at diagnosis was 46.7 +/- 13.2 years (range: 19 to 69 years). Tumors were grouped into three categories at the time of initial diagnosis: group 1, grossly malignant (four patients, or 7.5%); group 2, intermediate (partial capsular and/or subcapsular vascular invasion) (10 patients, or 18.5%); and group 3, benign appearing (40 patients, or 74%). Twenty-one (39%) of the patients had a history of low-dose, external radiation to the head and neck in childhood (including three of four grossly malignant lesions). A separate non-Hürthle cell thyroid carcinoma was found within the thyroid gland in 22 (50%) of the patients--79% were papillary and 21% were follicular carcinomas. In half of these, there was a history of childhood irradiation. During a mean follow-up period of 8.4 years (range, 22 days to 35 years), three additional Hürthle cell tumors were recognized as malignant after metastases were discovered--two were originally classified as intermediate lesions and one was in the benign-appearing group. Thus, seven of 54 of our patients (13%) had Hürthle cell carcinomas. One of the seven patients died of widespread metastases after 35 years, and the other six are currently free of disease. We believe that therapy of these lesions should be individualized. Total thyroid ablation (surgical procedure followed by radioiodine therapy) is appropriate for frankly malignant Hürthle cell cancers, for all Hürthle cell tumors occurring in patients who received low-dose childhood irradiation, for associated papillary or follicular carcinomas, and in those patients who exhibit partial capsular or subcapsular vascular invasion. On the other hand, single, well-encapsulated, benign-appearing Hürthle cell tumors may be treated by lobectomy and careful follow-up, since the chance that they will later exhibit malignant behavior is low (2.5% in our series and 1.5% among patients described in the recent literature).
Adenoma↗
Graves' disease and thyroid cancer.
The relationship between Graves' disease or its therapy and carcinoma of the thyroid remains uncertain. We studied 20 patients found to have thyroid cancer in glands previously treated for Graves' disease between 1961 and 1986 at the University of Chicago Medical Center. Sixteen (80%) occurred in women and four (20%) occurred in men. The mean age at operation was 37 years (range, 19 to 69 years) and did not differ by sex. Fifteen of the 20 cancers (75%) were papillary while five (25%) were follicular. Six individuals (30%) had a history of external radiation to the head and neck as an infant, child, or young adult. Two others had received radioiodine (RAI) therapy for Graves' disease 1 and 19 years earlier. Patients were divided into three groups: group I: four patients (20%) had a neck mass 4, 14, 20, and 41 years after having had a subtotal thyroidectomy (STT) for Graves' disease; three of four had a history of external irradiation therapy. These tumors behaved aggressively, resulting in the death of two of the four patients. group II: 11 patients (55%) had diffusely enlarge toxic goiters without a nodule. A carcinoma was diagnosed intraoperatively on frozen section in only two of these patients. The others received STT. After recognition on permanent section, those carcinomas that were 4 mm or greater in diameter received postoperative RAI. One recurrence occurred and was treated successfully with further RAI. group III: Five patients (25%) had Graves' disease and a palpable thyroid nodule. None of them had had a prior thyroidectomy for Graves' disease, as in group 1. Thyroid carcinoma was diagnosed in all patients preoperatively or intraoperatively, and a total thyroidectomy was performed. Each patient is alive and well with a mean follow-up of 5 years. Between 1971 and 1981, 194 patients had surgery for Graves' disease, and 10 (5.2%) were found to have an associated carcinoma; six patients (3.1% of the total) did not have a nodule or any other suspicion of malignancy before surgery. During the same time, 303 patients received RAI therapy for Graves' disease and one (0.3%) has subsequently developed thyroid carcinoma. Thyroid cancer associated with Graves' disease is found more commonly in surgically treated patients than in patients after RAI therapy. The greatest risk factor in our patients was previous external radiation to the head and neck. Such individuals should be treated with total thyroid ablation rather than the usual STT, since they are at risk of developing aggressive thyroid cancers if thyroid remnants are left.
Adult↗
Cisplatinum and bleomycin for advanced or recurrent squamous cell carcinoma of the head and neck: a randomised factorial phase III controlled trial.
A phase III 2 X 2 factorial trial of cisplatinum and bleomycin in 116 patients with recurrent or advanced squamous cell carcinoma of the head and neck is reported. Thirty percent of patients proved to be unfit for chemotherapy, and of those treated progression of tumour was the commonest "response". However, 25% of patients achieved a partial or complete response, with no significant difference in response rates between the treated arms. The median number of courses received was 1 (range 0-6) and the commonest causes for discontinuation of treatment were renal toxicity and death. Bleomycin reduced survival, but not significantly so, whereas cisplatinum prolonged median survival significantly by 10 weeks. Significant predictors of survival, in addition to treatment by cisplatinum, were age, performance status, N status, number of courses and response of the tumor.
Aged↗
Cointegrates carrying two copies of a Tn3 derivative in an inverted orientation.
We constructed a mutant of Tn3, Tn3 #2, that contains a 55-bp direct repeat of sequences near the amino-terminal coding region of the transposase, and an 8-bp EcoRI linker. This mutant transposase is functional. The plasmid carrying Tn3 #2, pMB8::Tn3 #2, recombines with the plasmid pHS1 at a frequency of 2.8 X 10(-7) recombinants per division cycle. This is similar to the recombination frequency of pHS1 and pMB8::Tn3+ (wild-type) which is 4.5 X 10(-6) recombinants per division cycle. One-third of the recombinants between pMB8::Tn3 #2 and pHS1 were approx. 22 kb in length. Restriction analysis and nucleotide sequencing showed that these large plasmids were Tn3 #2-mediated cointegrates formed by integration of pMB8::Tn3 #2 into pHS1. However, unlike Tn3 tnpR- -mediated cointegrates that contain direct repeats of the incoming element, Tn3 #2-mediated cointegrates carry two copies of Tn3 #2 in the form of inverted repeats. Like the tnpR- repeats, the Tn3 #2 repeats occur at both junctions between the parental plasmids, and are associated with a 5-bp direct duplication of the pHS1 target site. Furthermore, these recombinants contain a small deletion starting precisely at the end of Tn3 #2 and extending into pMB8 sequences. We propose a model for the generation of Tn3 #2-mediated cointegrates.
Base Sequence↗
The impact of lithium in South-West Scotland. III. The discontinuation of lithium.
A review in South-West Scotland of all patients prescribed lithium for the first time during the years 1972-82 showed that on average, 12 per 100,000 of the general population start this drug each year. By the end of the period, lithium had been stopped in 58% of patients; the most common reason for discontinuation was the development of side-effects, of which tremor was the most frequent. In only 15% was lithium stopped as it was considered no longer necessary; 44% of patients discontinued lithium within one year of starting it.
Adult↗
Trans-acting factors are responsible for the lack of beta-globin gene expression in K562 cells.
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Acetyltransferases↗
Styles of care provided to children in the United States: a comparison by physician specialty.
This study was based on findings from a national survey of physicians that was conducted from 1975 to 1977. The data concern face-to-face encounters with children in the ambulatory care setting. Over one half of the practices of pediatricians consisted of infants and preschoolers, whereas well over 50 percent of the child patients of other types of physicians were 10 to 19 years old. The proportion of visits dealing with a problem already under care was consistently greater for specialists other than primary care physicians; the proportion of visits for preventive care was much lower in the practices of these specialists than in primary care practice. These findings suggest that other specialists are functioning in ways different from primary care physicians. As compared with family physicians, pediatricians performed more diagnostic tests for all diagnoses and more immunizations and counseling about growth and development, were more likely to have seen children previously for problems other than the one dealt with in the visit under consideration, and were more likely to report that no specific therapy was required (except for well-child care). However, family physicians did more counseling about family and sex matters than pediatricians, were much more likely to have seen musculoskeletal and skin problems among 10- to 19-year-old patients, and were much more likely to have administered cauterization, cryotherapy, or suturing for skin problems. Family physicians provided more counseling of all types and did more minor surgical procedures than general practitioners. These and other findings show the existence of systematic differences across specialties in the care of children, even for apparently similar problems.
Acute Disease↗
Long-term follow-up study of compensated low-dose 131I therapy for Graves' disease.
We treated 187 patients who had Graves' disease with low-dose radioactive iodide (131I), using a protocol that included a compensation for thyroid size. The incidence of early hypothyroidism (12 per cent) was acceptably low in the first year after 131I treatment, but we found a cumulative high incidence (up to 76 per cent) at the end of the 11th year. In contrast, the incidence of permanent hypothyroidism was relatively stable in 166 surgically treated patients, increasing from 19 to 27 per cent at the end of 11 years. Among 122 medically treated patients, only 40 per cent entered remission, and hypothyroidism developed in 2 per cent during the same period of follow-up. The long-term incidence of hypothyroidism in our patients treated with low-dose 131I therapy was much higher than that found in earlier studies using a comparable dose. Our study suggests that it will be difficult to modify therapy with 131I alone to produce both early control of thyrotoxicosis and a low incidence of hypothyroidism.
Adult↗
A 37 X 10(3) molecular weight plasmid-encoded protein is required for replication and copy number control in the plasmid pSC101 and its temperature-sensitive derivative pHS1.
Nucleotide sequences were determined for a region essential for autonomous replication and partitioning of pSC101, a plasmid whose replication is dependent on the Escherichia coli dnaA gene product. The essential replication region contains one long coding sequence, rep101 , for a protein composed of 316 amino acids, and a polypeptide approximately 37 X 10(3) Mr in size was identified as the rep101 gene product. rep101 is preceded by two inverted repeat sequences, three directly repeated sequences and a region of high A + T content containing a sequence similar to the E. coli oriC consensus sequence. Because the lesions in seven replication-deficient insertion mutants, four mutants with increased copy number and one temperature-sensitive replication mutant occur within rep101 , the rep101 gene product must control pSC101 replication and copy number. par, a region adjacent to the replication region, which functions in stable plasmid inheritance, contains several inverted repeat sequences.
Autoradiography↗
Who provides health care to children and adolescents in the United States?
Face-to-face visits by children and adolescents in office-based practice in the mid-1970s were studied. Pediatricians, family physicians, and general practitioners accounted for 35%, 6%, and 30%, respectively, of all child visits. Although 40% to 45% of preventive and medical encounters were with pediatricians, only 12% of visits for minor surgery, 20% of visits for psychosocial problems, and 9% of visits for combined medical-surgical reasons were to pediatricians. Only in very young children did pediatricians provide a substantial proportion of care for each of the types of visits. For some common diagnoses (acne, refractive error) most care was provided by specialists other than primary care specialists, but less than 16% of all preventive care visits (including routine eye examinations) was provided by specialists other than primary care physicians. A substantial proportion of the prenatal care and management of minor trauma was provided by family physicians and general practitioners. Although the limitations of the study (including an average response rate of 55%, exclusion of certain specialties and institutional physicians, sampling at different times of the year, lack of control for area of location of practice, and lack of information about response rates of different types of physicians within each specialty) preclude definitive conclusions, the findings raise important questions for future study.
Adolescent↗
A profile of pediatric practice in the United States.
We profiled pediatric practice in the United States through a second-order analysis of data gathered in 1977 from 429 practicing pediatricians. Age, sex, board certification status, practice arrangement, and practice location of pediatricians in the United States were evaluated, as well as their patterns of practice. The number of and reasons for visits made to pediatricians by patient age and sex were tabulated. Child health supervision and diseases of the upper and lower parts of the respiratory tract accounted for 84.5% of the principal diagnoses made in 21,784 visits to the sample of pediatricians studied. These data may be useful in planning pediatric primary care residency training program curricula and in making planning decisions regarding the number and distribution of pediatricians nationally.
Adolescent↗
Which children with febrile seizures need lumbar puncture? A decision analysis approach.
Whether all children brought to the emergency room with a first seizure and fever require lumbar puncture (LP) remains controversial. We reviewed the emergency room records of 241 children aged 6 months to 6 years who had this clinical picture. Five history and physical examination items discriminated between children with and without meningitis: a physician visit within 48 hours before the seizure; the occurrence of convulsions on arrival at the emergency room; a focal seizure; suspicious findings on physical and/or neurologic examination. Used in combination, these items (risk factors) identified all children with meningitis but would have spared 62% of children without meningitis the need for LP. In a decision analysis framework, they were as sensitive but more specific than LP in detecting children with meningitis. Most important, their negative predictive value was 100%.
Child↗