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Biomedical subjects

M Carter

Publications and source records attributed to M Carter.

At least 19 recordsLinked to original sources

The identification of a domain in Escherichia coli elongation factor Tu that interacts with elongation factor Ts.

A method has been developed to search for the elongation factor Tu (EF-Tu) domain(s) that interact with elongation factor Ts (EF-Ts). This method is based on the suppression of Escherichia coli EF-Tu-dominant negative mutation K136E, a mutation that exerts its effect by sequestering EF-Ts. We have identified nine single-amino acid- substituted suppression mutations in the region 146-199 of EF-Tu. These mutations are R154C, P168L, A174V, K176E, D181G, E190K, D196G, S197F, and I199V. All suppression mutations but one (R154C) significantly affect EF-Tu's ability to interact with EF-Ts under equilibrium conditions. Moreover, with the exception of mutation A174V, the GDP affinity of EF-Tu appears to be relatively unaffected by these mutations. These results suggest that the domain of residues 154 to 199 on EF-Tu is involved in interacting with EF-Ts. These suppression mutations are also capable of suppressing dominant negative mutants N135D and N135I to various degrees. This suggests that dominant negative mutants N135D and N135I are likely to have the same molecular basis as the K136E mutation. The method we have developed in this study is versatile and can be readily adapted to map other regions of EF-Tu. A model of EF-Ts-catalyzed guanine-nucleotide exchange is discussed.

Amino Acid Sequence

A spliced intron accumulates as a lariat in the nucleus of T cells.

The vast majority of mammalian genes are interrupted by non-coding segments of DNA termed introns. Introns are spliced out of RNA transcripts as lariat structures, and then are typically debranched and rapidly degraded. Here, we described an unusual spliced intron from the constant region of the T cell receptor-beta (TCR-beta) locus that is relatively stable in mammalian cells. This intron, IVS1C beta 1, accumulates as a set of lariat RNA structures with different length tails in the nucleus of T cells. The accumulation of this spliced intron is developmentally regulated during murine thymocyte ontogeny. The property of stability appears to be evolutionarily conserved since the human version of this intron also accumulates in T cells. The stability is selective since other spliced TCR-beta introns do not detectably accumulate in T cells. The unusual stability of this intron does not depend on T cell specific factors since non-T cells transfected with TCR-beta gene constructs also accumulate spliced IVS1C beta 1. The discovery of a mammalian intron that accumulates as a lariat in vivo provides an opportunity to elucidate mechanisms that regulate intron debranching, stability, and nuclear localization.

Animals

Manipulation of phototransductive membrane turnover by crab photoreceptors in vitro: effects of two protein kinase activators, SC-9 and phorbol ester in the presence of a protein phosphatase inhibitor, okadaic acid.

1. Retinae of crabs, Leptograpsus variegatus, held on a 12:12 h light-dark cycle were prepared for culture in vitro shortly before light-off. After an hour in darkness to permit the assembly of "night" rhabdoms, retinae were exposed to various combinations of drugs: 1 microM okadaic acid (OKA); 60 microM SC-9; 10 microM phorbol, 12,13-diacetate (PDA). 2. The effects of the specific protein phosphatase inhibitor, OKA, are confirmed as light-dependent. Rhabdom sizes were not compromised by OKA, nor by either of the two protein kinase activators, SC-9 or PDA when each was deployed alone in darkness. 3. In combination with OKA, PDA induced demolition of rhabdoms by abnormal macropinocytosis of microvillar membranes. 4. Combined with OKA, SC-9 induced a transient reduction of rhabdoms, followed by overgrowth to abnormal sizes. Overgrowth was blocked by the transcription inhibitor actinomycin D. 5. Disparate consequences of combining OKA with SC-9 or PDA imply that more than one protein kinase C may be involved.

Animals

Sonographic characteristics of the urethrovesical anastomosis in the early post-radical prostatectomy patient.

It is possible that the advent of more aggressive surgical approaches to carcinoma of the prostate, including neoadjuvant and adjuvant therapy, will lead to a higher incidence of pelvic recurrence rates in coming years. A method of sequentially monitoring the region of the urethrovesical anastomosis for early recurrence that is more accurate than digital rectal examination is required. Transrectal ultrasound is an established technique for the preoperative assessment of prostate cancer. It has also been used postoperatively to guide a biopsy needle into palpably suspicious areas at the urethrovesical junction or for random biopsies in patients with elevated prostate specific antigen levels. However, the sonographic anatomy of the postoperative urethrovesical junction has not previously been described. In this prospective study we analyze the transrectal sonographic characteristics of the neoanatomy in 30 patients, all within 3 months following surgery for clinically intracapsular disease. We describe features of the neoanatomy, such as anterior tissue nodules and anastomotic rings. Because of distinct variations in the neoanatomy of different patients we recommend early postoperative transrectal biplanar sonography to establish a baseline image for each individual case. This would be useful for later comparison and may prevent a false positive scan on subsequent followup studies.

Adenocarcinoma

A method of predicting adult height and obesity in long-term survivors of childhood acute lymphoblastic leukemia.

PURPOSE: Short stature and obesity have been reported among long-term survivors of childhood acute lymphocytic leukemia (ALL). We examined factors that contribute to these adverse sequelae. PATIENTS AND METHODS: Serial height and weight measurements were analyzed for 91 long-term survivors who were treated for ALL between 1967 and 1975 at a single institution. These patients were all younger than 12 years at diagnosis, were in continuous complete remission, had reached final height, and had height and weight measurements within 1 year of age 18 years. They had received craniospinal (n = 33) or cranial irradiation (n = 58) to total doses of 24 Gy as CNS prophylaxis. Standard deviation scores (SDS) were used to reflect the deviation of height and weight measurements from population means, and the body mass index (BMI; weight divided by height squared) was used in assessing obesity at age 18 years. RESULTS: Short stature (less than fifth percentile) was seen in 41 patients (45%), and obesity (BMI greater than or equal to 24 kg/m2) in 35 (38%). Regression formulae were developed that explain 65% and 62% of the variability in patient height and BMI, respectively. CONCLUSIONS: Risk factors were identified for abnormally short stature, which was defined to be a decrease of 1.5 SDS in height from diagnosis to age 18 years. These factors include younger age and above-average height for age at diagnosis (height SDS greater than 0), craniospinal irradiation, and greater decrease in height SDS during antileukemic therapy. Risk factors for obesity at age 18 years include weight SDS greater than 0 and greater than height SDS at 1 year after the end of chemotherapy.

Adolescent

Long-term survivors of leukemia treated in infancy: factors associated with neuropsychologic status.

PURPOSE: Because of concerns about late toxicities of treatment among infants diagnosed with acute lymphoblastic leukemia (ALL), and especially the effects of cranial radiation therapy (CRT), we compared the functional and neuropsychologic status of 26 long-term survivors of ALL who were diagnosed in the first 24 months of life versus 26 children who were treated previously for Wilms' tumor. PATIENTS AND METHODS: Of the children with ALL, CNS prophylaxis included no CRT in six, 18 Gy CRT in five, 20 Gy CRT in seven, and 24 Gy CRT in five. Three additional children experienced CNS relapse and received total CRT doses of 24, 40, and 44 Gy. All children received neuropsychologic testing; children with ALL also participated in diagnostic imaging studies. RESULTS: As a group, the children who were treated for ALL did not differ significantly from those who were treated for Wilms' tumor on objective measures of global functional status. However, children treated for ALL had a significantly lower mean intelligence quotient (IQ) (87 v 96), poorer performance on four of six measures of visual and auditory memory, lower achievement with regard to arithmetic skills, and a greater frequency of special educational intervention than those who were treated for Wilms' tumor. IQ and auditory memory performance in the ALL group was correlated inversely with time since the completion of therapy and total CRT dose. CONCLUSIONS: These results reinforce the contemporary trend of prophylactic CRT omission in very young children except for those who are at risk for CNS relapse. For infants and very young children who require CRT, evidence is presented that supports the approach for the delay of CRT until the child is older.

Adolescent

Treatment of adult acute lymphoblastic leukaemia (ALL) over a 16 year period.

Between 1972 and 1988 269 newly diagnosed adolescents and adults (age range 14-78 years) with ALL were managed with three protocols of increasing intensity (OPAL, HEAV'D, OPAL-HDAraC). The complete remission (CR) rate in 212 patients treated with OPAL and HEAV'D was 151/212 (71%), the median CR duration was 1.9 years. With a median follow-up of 9 years, 49 patients remain free of disease. On multivariate analysis age, blast cell count, and immunophenotype were found to correlate significantly with CR rate, remission duration and survival. CR was achieved in 38/57 (67%) patients subsequently treated with OPAL-HDAraC; however, although remission duration was longer in 'high risk' patients (T, B and Null phenotype irrespective of blast cout, cALLA+ve with blast count greater than 10 x 10(9)/l) as compared to the results achieved in similar patients with OPAL/HEAV'D, overall, the results were no better than those achieved previously. Indeed, patients in the 'standard risk' category (cALLA+ve, blast count less than 10 x 10(9)/l) fared better previously. Subsequently, neither treatment according to prognostic variables, or the addition of different pairs of drugs in rotation, to HEAV'D, have improved outcome in 63 other patients. Currently, further intensification of the early treatment is being evaluated.

Adolescent

Chemical weapons.

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Anesthetics

Family psychoeducation, social skills training, and maintenance chemotherapy in the aftercare treatment of schizophrenia. II. Two-year effects of a controlled study on relapse and adjustment. Environmental-Personal Indicators in the Course of Schizophrenia (EPICS) Research Group.

We demonstrated earlier that a novel family psychoeducational approach and an individual social skills training approach designed for patients living in high-expressed emotion households each reduced schizophrenic relapse by one-half when compared with medication controls in the 1st year after hospital discharge. The combination of treatments resulted in no relapse. Results have now been obtained after 2 years of continuous treatment. By 24 months, a persistent and significant effect of family intervention on forestalling relapse was observed, but the effect of social skills training was lost late in the 2nd year. There was no additive effect on relapse that accrued to the combination of treatments. Beyond 2 years, however, the effect of family intervention was likely compromised as well. Treatment effects on the adjustment of survivors were circumscribed, due, in part, to study design characteristics. Effects generally favored the social skills-alone condition at 1 year and the family condition or combined family/social skills condition at 2 years.

Adult

The distribution of actin immunoreactivity in rhabdomeres of tipulid flies in relation to extracellular membrane shedding.

Rhabdomeres of tipulid flies lose membrane during turnover from a 'shedding zone' composed of microvillar tips. These distal domains lack intramicrovillar cytoskeletons and appear to be empty sacs of membrane. Recent concerns about the role of ninaC mechano-enzymes in the architecture of dipteran rhabdomeral microvilli and the dynamic role that they may play in the creation of shedding zones demand an examination of the distribution of actin in tipulid rhabdomeres. We compared rhabdomeres from tipulid retinae incubated before fixation for immunocytochemistry in a buffer without additives and a stabilising buffer that contained a cocktail of cysteine protease inhibitors; both were challenged by an anti-actin antibody for immunogold labelling after embedding in LR White Resin. Shedding zones thus processed collapse to structureless detritus. Stabilised and unstabilized shedding zones were immunonegative to anti-actin. To ensure that the negative results were not consequent upon conformational changes generated by the processing protocol, we examined microvilli of degenerating rhabdomeres of the Drosophila light-dependent retinal degeneration mutant rdgBKS222 (which separate and collapse without creating a shedding zone) and found the detritus they generate to be immunopositive to anti-actin. Stabilised and unstabilized regions of basal regions of tipulid rhabdomeres were equally immunopositive. We infer that (a) actin is absent from shedding zones; (b) actin is not degraded by microvillar cysteine proteases. The implications of these conclusions are discussed in relation to some functional models of arthropod photoreceptor microvilli.

Actins

Reducing the effects of adjacent distractors by narrowing attention.

Three experiments explored the gradual narrowing of visual attention to a letter target when other letters were positioned close by. The method by which attention was narrowed involved presenting a digit target immediately prior to the latter target and in the same location for progressively shorter durations and requiring the subject to identify both the digit target and the letter target before responding. The response time data from the first 2 experiments indicated that shorter durations of the digit reduced the amount of information processed from noise letters positioned on either side of the letter target. In the third experiment, in which separation of letters was increased slightly, the response times indicated that the information from flanking noise letters may have been virtually eliminated.

Adult

Mental function after general anaesthesia for transurethral procedures.

We have assessed the influence of age and preoperative mental status score on postoperative mental function, using a choice reaction time test. One hundred and twelve patients (mean age 70 yr, range 48-88 yr) were given a standardized general anaesthetic for transurethral procedures. Mental status before anaesthesia was measured with the Clifton Assessment Procedure for the Elderly (CAPE). Reaction time was measured before anaesthesia and for up to 3 days after anaesthesia. Variability in reaction time performance was increased 24 h after anaesthesia in transurethral patients, but not in a control group of orthopaedic patients (P = 0.0006). Factors contributing to increased variability of reaction time after operation in a multiple regression analysis were reduced CAPE score before operation (P less than 0.0001), extent of surgery (P = 0.023), postoperative pain (P = 0.007) and postoperative sedative drugs (P = 0.009). Factors not contributing included age, diagnosis of cancer, number of previous operations in past 5 years, duration of anaesthesia, minimum mean arterial pressure, minimum and maximum perioperative PCO2 values, postoperative pyrexia and poor sleep.

Aged

Abnormal growth patterns and adult short stature in 115 long-term survivors of childhood leukemia.

Significant growth retardation was found in 115 survivors of childhood acute lymphoblastic leukemia (ALL) who had completed their growth. These children were diagnosed before 12 years of age and treated on four protocols in a single institution; all received either cranial (n = 78) or craniospinal (n = 37) prophylactic irradiation. Patients' heights at diagnosis were within expected ranges, but final heights were greater than or equal to 1 SD below population means in 74% of cases and greater than or equal to 2 SD in 37%. Effects on growth were more pronounced for children who had received craniospinal irradiation, but decrements were also significant in the cranial irradiation group, with adult heights greater than or equal to 2 SD below population norms in 32%. Growth retardation was significantly greater (P less than .0001) in children who had earlier disease onset. Growth deceleration occurred not only during chemotherapy but during a later period that followed an interval of improved growth in many cases. Thus, late decrements in growth may be missed in studies that do not follow patients until they have attained final heights. These findings indicate that abnormally short stature among survivors of ALL merits further clinical and research attention.

Antineoplastic Combined Chemotherapy Protocols

Characterization of immunoglobulin heavy chain genes from an acute lymphocytic leukemia with four rearrangements.

Approximately 25% of acute leukemias of the B-cell lineage demonstrate more than two rearranged immunoglobulin heavy chain genes when examined by Southern blot analysis. The origin of the extra bands was investigated by molecular cloning and sequencing of four rearranged genes from one patient's leukemic cells. All four rearrangements were apparently derived independently. Two of the rearrangements used the VH6 variable region, attached to different diversity and joining regions. One of the two rearrangements contained a mutation in the coding sequence leading to the generation of a nonsense codon. This rearranged gene also differed from the other VH6 containing gene starting at about 330 bp upstream of the ATG initiation codon. The third rearranged gene used a member of the VH2 variable gene family. A DH-JH rearrangement was found in the fourth rearranged gene. The data indicate that the leukemia probably arose as a result of the transformation of an early B-cell progenitor that lacked rearranged immunoglobulin genes but retained some differentiation potential.

Blotting, Southern

The t(10;11)(p14;q21) translocation in three children with acute myeloblastic leukemia.

A total of 161 cases of pediatric de novo acute myeloblastic leukemia (AML) have been reviewed, for which complete karyotyping was available and three cases (2%) were identified with t(10;11)(p14;q21). Two of the three children were infants with monoblastic (FAB M5) leukemia and the third was an adolescent with undifferentiated myeloid (FAB M1) leukemia. Both infants presented with increased levels of lactate dehydrogenase. None of these cases had increased eosinophils. One of the infants is in remission 18+ months after diagnosis and intensive chemotherapy; the two other children attained brief initial remissions but succumbed to their disease within 11 months of diagnosis. The prognosis of such children appears to be similar to that of cases of AML lacking this translocation.

Adolescent

Whey protein hydrolysate formula for infants with gastrointestinal intolerance to cow milk and soy protein in infant formulas.

Twenty-one infants less than 6 months of age with gastrointestinal symptoms of cow milk and/or soy protein-based infant formula intolerance (diarrhea in 14, hematochezia in 16, emesis in 8, failure to thrive in 4, and colic in 10) were treated clinically with a whey protein hydrolysate formula. Six patients improved when placed directly on the formula, and 15 remained asymptomatic or improved when given the whey hydrolysate formula following initial treatment with a casein hydrolysate or elemental formula. Eighteen had supporting evidence of an allergic basis for their symptoms, including a family history of allergies in 6, a clinical challenge with the offending formula in 1, laboratory tests consistent with atopy in 11, and/or rectal biopsy with histologic allergic features in 7. The whey hydrolysate formula may be an acceptable alternative to soy or casein hydrolysate formulas in most infants with gastrointestinal symptoms of cow milk and/or formula intolerance.

Food Hypersensitivity

The "Carpentier" thoracic aortic by-pass technique for management of descending aortic aneurysms and dissections--a radiological perspective.

The "Carpentier" thoracic aortic bypass procedure is a recently described and, until now, little used surgical technique for the treatment of descending thoracic aortic aneurysms and dissections. It involves the placement of a large conduit from the ascending aorta to the distal abdominal aorta through a midline sternotomy incision extended to the umbilicus and the subsequent interruption of the aorta just distal to the left subclavian artery via a left postero-lateral thoracotomy. As radiologists we should be aware of this alternative surgical option so that, in addition to diagnosing and classifying these aneurysms and dissections, we can assist our surgical colleagues in:-- a. The pre-operative assessment of the aorta for bypass grafting including the distal abdominal aorta b. The post-operative monitoring of the anticipated thrombotic occlusion of the descending thoracic aorta to the coeliac axis.

Aged