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Biomedical subjects

M A Sullivan

Publications and source records attributed to M A Sullivan.

At least 19 recordsLinked to original sources

83-kilodalton heat shock proteins of trypanosomes are potent peptide-stimulated ATPases.

A Crithidia fasciculata 83-kDa protein purified during a separate study of C. fasciculata trypanothione synthetase was shown to have ATPase activity and to belong to the hsp90 family of stress proteins. Because no ATPase activity has previously been reported for the hsp90 class, ATP utilization by C. fasciculata hsp83 was characterized: this hsp83 has an ATPase kcat of 150 min-1 and a Km of 60 microM, whereas the homologous mammalian hsp90 binds ATP but has no ATPase activity. Crithidia fasciculata hsp83 undergoes autophosphorylation on serine and threonine at a rate constant of 3.3 x 10(-3) min-1. Similar analysis was performed on recombinant Trypanosoma cruzi hsp83, and comparable ATPase parameters were obtained (kcat = 100 min-1, Km = 80 microM, kautophosphorylation = 6.3 x 10(-3) min-1). The phosphoenzyme is neither on the ATPase hydrolytic pathway nor does it affect ATPase catalytic efficiency. Both C. fasciculata and T. cruzi hsp83 show up to fivefold stimulation of ATPase activity by peptides of 6-24 amino acids.

Adenosine Triphosphatases

Roentgenographic evaluation of the augmented breast.

We performed a retrospective study to determine the sensitivity of mammography in detecting breast cancer arising in women with augmented breasts. Of eight women with breast implants in whom breast cancer developed, six had mammograms before biopsy. Only two of the six cancers were identified mammographically (sensitivity = 33%), and one of these two was seen only in retrospect. In both cases, the mammographic findings suggested a benign rather than a malignant process. All eight women had a palpable mass and early disease, and all are clinically disease-free at present. The sensitivity of mammography in detecting palpable cancers in a control group of women without implants was 92% (118 of 128). For tumors of 2 cm or less, the sensitivity was 88% (58 of 66). These results suggest that the sensitivity of mammography in detecting breast cancer is decreased when implants are present. Further investigations are needed to determine the effects of prostheses on mammographic evaluations.

Adult

Fear of AIDS related to development of obsessive-compulsive disorder in a child.

Fear of acquired immune deficiency syndrome (AIDS) has been associated with a variety of psychiatric disorders in adults and in some adolescents. A case is reported of a child with an unrealistic fear of AIDS who developed an obsessive-compulsive disorder. This case illustrates the importance of providing adequate AIDS information to children.

Acquired Immunodeficiency Syndrome

Cloning and expression in Escherichia coli of a hypoxanthine-guanine phosphoribosyltransferase-encoding cDNA from Plasmodium falciparum.

The enzyme hypoxanthine-guanine phosphoribosyltransferase (HGPRT) of Plasmodium falciparum plays a key role in the salvage of preformed purine nucleotides from parasite-infected erythrocytes. Since P. falciparum cannot synthesize purines de novo, development of inhibitors specific for the parasite HGPRT should be an effective method of chemotherapy. To provide sufficient amounts of HGPRT for biochemical and crystallographic analysis, we have isolated the P. falciparum HPRT cDNA sequence and expressed it in an Escherichia coli strain deficient for both de novo purine synthesis and guanine utilization (strain GP120). GP120 cells containing the P. falciparum HPRT plasmid vector (pRD500), when grown in the presence of isopropyl-beta-D-thiogalactopyranoside (IPTG) which induces the tac promoter of the expression vector, produce a novel protein of 26 kDa, which is in agreement with the predicted Mr deduced from the HPRT cDNA open reading frame. In addition, we have demonstrated significant HGPRT activity in cell-free extracts of GP120[pRD500] cultures grown in minimal medium containing xanthine, as the sole source of purines, and IPTG.

Amino Acid Sequence

Dental abnormalities and bone lesions associated with familial adenomatous polyposis: report of cases.

Dental abnormalities and bone lesions of the maxilla and mandible are found in more than 70% of patients with familial adenomatous polyposis (FAP). Dental abnormalities include impacted teeth (other than third molars), supernumerary teeth, congenitally missing teeth, and fused roots of molars. Bone lesions consist of osteomas--isolated or in clusters--in the maxilla and mandible. In this study of 24 patients, 75% had demonstrable dental abnormalities, and 79% had osteomas of the maxilla and mandible. Because dental abnormalities and bone lesions are present early in life, these features may be helpful in diagnosing this syndrome.

Adenomatous Polyposis Coli

Usefulness of duplex ultrasound in evaluating vertebral arteries.

A criticism of duplex scanning of the carotid vessels is that the study is limited to evaluation of the carotid bifurcations, whereas with other vascular imaging studies the vertebral vessels can also be seen. We have prospectively collected data on our ability to evaluate the vertebral vessels on all patients who are sent for carotid evaluations. We have scanned 677 patients and have identified flow in one or both vertebral arteries in nearly 90% of these patients. Therefore, we urge that evaluation of vertebral vessels be made a routine part of the standard carotid duplex ultrasound examination.

Carotid Artery Diseases

The identification of ulcerative plaque with high resolution duplex carotid scanning.

A retrospective study evaluated 50 patients who had pathologically proven intraplaque hemorrhage. The patients were pathologically divided into two groups by the presence or absence of intimal ulcerations. These two groups were then sonographically compared with regard to surface characteristics of the plaque, plaque size, size of the sonolucent area within the plaque, and location of the sonolucent area relative to the intimal surface. No defined sonographic characteristics could be used to separate these two groups of patients with heterogeneous plaques into those who had or did not have ulcerations. Most importantly, merely sonographically evaluating the surface of the plaque to determine if it was smooth or irregular could not be used as a successful means to identify which patients were at risk for ulceration.

Arteriosclerosis

Transcription of eucaryotic tRNA1met and 5SRNA genes by RNA polymerase III is blocked by base mismatches in the intragenic control regions.

We have constructed duplex DNAs containing single G-T or A-C mismatches in the X. laevis tRNA1met gene. Mismatches within regions of this gene which are bound by transcription factor TFIIIC prevent transcription by RNA polymerase III. Homoduplexes with G-C----A-T mutations at some of the same sites, however, are transcribed efficiently in oocytes. Mismatches outside of the tRNA1met gene have no effect upon transcription. A survey of several point mutants in the Syrian hamster 5SRNA gene indicates that mismatches outside the internal control region somewhat reduce transcription, but a mismatch within the internal control region blocks transcription. Thus, the presence of mismatched bases in the region of DNA which interacts with RNA polymerase III transcription factors blocks transcription, perhaps by interfering with DNA renaturation following transit of the RNA polymerase.

Animals

Ultrasonic evaluation of the stomach, small bowel, and colon.

A characteristic sonographic pattern that suggests a bowel lesion is pathologically significant in over 90% of patients with this pattern. The authors call this pattern the "pseudokidney sign" because it superficially resembles the ultrasonic appearance of the kidney. Although found occasionally in normal persons, this characteristic pattern should always lead the sonographer to consider a bowel lesion. Additional radiographic examinations, such as an upper-gastrointestinal series, small-bowel studies, and barium-enema examinations, are advised for definitive diagnosis.

Adult

Colonic myoelectrical activity in irritable-bowel syndrome. Effect of eating and anticholinergics.

To determine the effect of a standard meal on colonic myoelectrical and motor activity in the irritable-bowel syndrome and to determine the effect of a single dose of an oral anticholinergic drug (clidinium bromide) on this response, we studied 10 patients. These patients showed a prolonged increase in both colonic spike (P less than 0.05) and motor activity (P less than 0.05) after eating as compared to normal subjects. Clidinium did not affect the frequency of colonic slow waves or the basal colonic spike and motor activity. However, the anticholinergic reduced the prolonged postprandial colonic spike and motor response in the patients and also reduced the postprandial increase in colonic contractions at 3 cycles per minute (P less than 0.05). These studies indicate that patients with the irritable-bowel syndrome show an abnormally prolonged post-prandial increase in colonic spike and motor activity. An anticholinergic drug reduces the duration and the magnitude of this abnormal colonic response.

Administration, Oral

Gastrointestinal myoelectrical activity in idiopathic intestinal pseudo-obstruction.

We evaluated the myoelectrical and motor function of the esophagus, small intestine, colon and anal sphincter in four patients with chronic idiopathic intestinal pseudo-obstruction. All patients had aperistalsis of the esophagus, with incomplete relaxation of the lower esophageal sphincter after swallowing or balloon distension. Duodenal slow-wave frequency was normal at 11.4+/-0.3 (+/-S.E.M.) cycles per minute. The patients did not have a normal increase in duodenal spike or motor activity after intestinal distension, but duodenal activity increased after stimulation with intravenous secretin. Colonic slow-wave activities were present at two frequencies, 6.2+/-0.3 and 3.3+/-0.1 cycles per minute. Neostigmine administration increased both colonic spike and motor activity normally. These studies suggest that in this disorder, physiologic neural responses to swallowing or intestinal distension are impaired but the intestinal smooth-muscle slow-wave activity and the spike and motor responses to exogenous neurohormonal stimulation are intact.

Adult

An approach to head, neck and trunk stabilization and control in cerebral palsy by use of the Milwaukee brace.

This paper reports the successful use of the Milwaukee brace in nine children with cerebral palsy and lack of head, neck and body control. After an initial period of apprehension, the brace has been approved by the patients themselves, their families, teachers and therapists and has added greatly to the quality of life within the limits of the patients' abilities. Follow-up has ranged from three months to five years (mean 3 1/2 years) and no deleterious effects have been noted.

Adolescent