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Biomedical subjects

M Cooper

Publications and source records attributed to M Cooper.

At least 19 recordsLinked to original sources

The effect of suramin on laboratory tests of coagulation.

The antitrypanosomal drug suramin, which has recently been under investigation as a cancer chemotherapeutic agent, has previously been found to induce heparin-like anticoagulants in treated patients. In the currently reported work suramin is shown to have an additional anticoagulant activity that is due to direct effects of the drug on procoagulant proteins. The studies were conducted with pooled normal plasma treated in vitro with suramin and with plasma samples obtained from patients who had received the drug intravenously for 2 weeks. It is demonstrated that in plasma suramin inhibits factors V, VIII, IX, X, XI, and XII, while thrombin, prothrombin, and factor VII are unaffected. The inhibition of factor V is virtually irreversible, although the effect of suramin on the other factors is readily reversed by dilution.

Blood Coagulation

Degenerative disc disease in the lumbar spine: another cause for focally reduced activity on marrow scintigraphy.

A patient is presented in whom a focal reduction in marrow activity in the lumbar spine on both leucocyte and nanocolloid marrow scintigraphy was subsequently shown to be due to fatty infiltration of marrow in association with disc degeneration. Degenerative disease in the lumbar spine has not been previously described as a cause of abnormal bone marrow distribution by such means and needs to distinguished from a more serious pathology, such as malignant infiltration and vertebral infection, which it may mimic. In a retrospective review of 33 nanocolloid bone marrow and 117 leucocyte scintigrams, 8 showed a degree of reduced marrow activity in the lumbar spine consistent with that caused by degenerative changes.

Adult

The Candida albicans PMM1 gene encoding phosphomannomutase complements a Saccharomyces cerevisiae sec 53-6 mutation.

We have constructed an ordered-array genomic DNA library of the pathogenic dimorphic fungus Candida albicans which facilitates the rapid cloning of C. albicans genes by hybridisation. Using the Saccharomyces cerevisiae SEC53 gene encoding phosphomannomutase as a hybridisation probe we have cloned the C. albicans homologue, PMM1, and determined its sequence. This gene shows high similarity, both at the nucleotide (76.2%) and amino-acid (77.7%) level, to the S. cerevisiae SEC53 gene. We have used the C. albicans PMM1 gene, in single copy, to transform temperature-sensitive S. cerevisiae sec53-6 mutant cells, which are defective in PMM activity at 37 degrees C, to growth at 37 degrees C. The C. albicans PMM1 gene is thus the structural and functional equivalent of the SEC53 gene.

Autoradiography

Photodynamic therapy in the treatment of Bowen's disease.

BACKGROUND: The treatment of Bowen's disease in anatomically difficult areas or especially large lesions can challenge accepted modalities of treatment. OBJECTIVE: The purpose of this study was to illustrate the effectiveness of photodynamic therapy in the treatment of Bowen's disease. In addition, photodynamic therapy may be used as adjuvant therapy for difficult lesions. METHODS: Six patients with Bowen's disease in various anatomic sites were treated with photodynamic therapy. Four were in a difficult anatomic site, or were especially large, or both. Photofrin, 1.0 mg/kg, was administered intravenously and laser treatment was given approximately 48 hours later with the argon dye laser. Light was administered at a wavelength of 630 nm and the light dose ranged from 185 to 250 joules/cm2. Treatment was given by surface radiation only. RESULTS: Eight lesions were treated. All showed a complete response at 3 months (100%) and continue to show a complete response at 6 and 12 months. Morbidity was low; the most significant side effects were moderate pain and edema. Healing time varied depending on the size of the lesion. CONCLUSION: Photodynamic therapy is an effective and useful alternative for Bowen's disease, especially those lesions in anatomically difficult areas or those that are especially large.

Adult

Facial recognition: a cognitive study of elderly dementia patients and normal older adults.

Dementia patients' and normal elderlies' recognition of familiar, ordinary emotional and facial expressions was tested. In three conditions subjects were required to name the emotions depicted in pictures and to produce them while presented with the verbal labels of the expressions. The dementia patients' best performance occurred when they had access to the verbal labels while viewing the pictures. The major deficiency in facial recognition was found to be dysnomia related. Findings of this study suggest that the connection between the gnostic units of expression and the gnostic units of verbal labeling is not impaired significantly among the dementia patients.

Aged

The osmotic integrity of the yeast cell requires a functional PKC1 gene product.

Seven temperature-sensitive cell lysis (cly) mutant strains of Saccharomyces cerevisiae were isolated which lyse at the restrictive temperature on hypotonic but not on osmotically supported medium. The seven mutants fell into four complementation groups, CLY12 to CLY15. The wild-type CLY15 gene was isolated by complementation of the cly15 temperature-sensitive growth defect. Sequence analysis revealed that the complementing DNA fragment encoded a partial PKC1 gene, which has previously been isolated as an S. cerevisiae homolog of mammalian protein kinase C genes (D. E. Levin, F. O. Fields, R. Kunisawa, J. M. Bishop, and J. Thorner, Cell 62:213-224, 1990). Subsequent genetic analysis showed that CLY15 and PKC1 represent identical loci in the yeast genome. A truncated PKC1 gene encoding only the predicted catalytic domain of Pkc1p was able to complement pkc1 mutant strains. Similar to what has been reported recently (D. E. Levin and E. Bartlett-Heubusch, J. Cell Biol. 116:1221-1229, 1992), we observed that cells deleted for the PKC1 gene are viable when grown on osmotically stabilized medium but are osmotically fragile and lyse rapidly after a shift to hypotonic medium. As shown by light and electron microscopic examinations, the delta pkc1 strain exhibits many cells with a strongly elongated bud or chains of incompletely budded cells when grown on solid medium.

Culture Media

Suramin: a novel growth factor antagonist with activity in hormone-refractory metastatic prostate cancer.

PURPOSE: Suramin is known to inhibit the growth of malignant prostate carcinoma cells in vitro. This led us to evaluate the effectiveness of suramin in the treatment of 38 patients with prostate carcinoma refractory to hormone therapy. PATIENTS AND METHODS: Suramin was administered by continuous infusion at a rate designed to reach a peak of 300 micrograms/mL at the end of 14 days. Patients were given 8 weeks to recover from any toxicity before beginning the second cycle. Subsequent cycles were administered in the same manner except the starting dose rate was 280 mg/m2. RESULTS: In 17 patients with measurable soft tissue disease, three had complete disappearance of soft tissue disease for 4, 5, and 11 months, whereas three patients had a greater than or equal to 50% decrease in the sum of the products of the diameters of all measurable disease for greater than or equal to 1 month. Of these 17 patients, pretreatment prostate-specific antigen (PSA) decreased by 75% or more in five (29%) and normalized in one (6%). The remaining 21 patients had disease limited to bone, and only one of these experienced resolution of more than 50% of all lesions on bone scan. Of these 21 patients, pretreatment PSA decreased by 75% or more in eight (38%) and normalized in five (25%). Median time to progression for all patients was 26.3 weeks, and median survival was 42.3 weeks. Patients with bone involvement alone exhibited a better survival than patients with soft tissue involvement (P2 = .02). Survival was strongly correlated (P2 = .0001) with a decline in the pretreatment PSA of greater than or equal to 75% by the eighth week on therapy, with nearly an 85% survival at 1 year compared with a 20% survival for those whose pretreatment PSA did not decline by that amount. CONCLUSION: We conclude that suramin is an active agent in hormone-refractory prostate carcinoma.

Aged

Congenital subglottic hemangioma: frequency of symmetric subglottic narrowing on frontal radiographs of the neck.

OBJECTIVE: This study was undertaken to determine how often symmetric subglottic airway narrowing is present in cases of infantile subglottic stenosis and to determine if the radiographic finding has any association with the anatomic location of the hemangioma. MATERIALS AND METHODS: All cases (n = 12) of endoscopically proved subglottic hemangioma from 1976 to 1991 were collected from the records at Children's Hospital of Michigan. In 10 cases, high-kilovoltage magnification studies or frontal radiographs of the neck were available for review by two observers who classified the subglottic narrowing as either symmetric or asymmetric. The radiographic findings in these 10 cases were then compared with the location and extent of the lesion as described endoscopically. RESULTS: In 50% of cases (n = 5), narrowing of the subglottic airway was symmetric. In four of these the hemangioma was either situated on the posterior wall or was circumferential, and in the remaining one an associated marked fibrotic reaction to a lateral wall lesion was present. All other lesions were on the lateral wall, and asymmetric subglottic airway narrowing was consistently shown on radiographs. CONCLUSION: Our results show that subglottic hemangioma often manifests as a symmetric subglottic airway narrowing and that the anatomic location of the hemangioma appears to be associated with the appearance on radiographs.

Glottis

Incidental finding of endolymphatic stromal myosis during luteinizing hormone releasing hormone agonist therapy for suspected benign uterine myomata. A case report.

A 39-year-old woman with an enlarging myomatous uterus underwent a three-month course of luteinizing hormone releasing hormone (LHRH) agonist treatment. Despite a 50% reduction in uterine size, pathologic examination after uncomplicated hysterectomy revealed a low-grade endometrial stromal sarcoma. As the use of LHRH agonists for myoma reduction increases, delay in the diagnosis of sarcomatous disease will become more widespread. With current available diagnostic modalities, differentiation between sarcomatous and myomatous growth within the uterus is difficult. The possibility of delay in the diagnosis of unsuspected sarcoma when using LHRH agonists is an inherent and apparently unavoidable complication in some cases.

Adult

Characterization of in vitro translated human mineralocorticoid receptor. Structure and activation.

The structures of the unactivated and activated mineralocorticoid receptors have been difficult to characterize because of receptor lability and steroid dissociation. Therefore, human mineralocorticoid receptor mRNA was translated in rabbit reticulocyte lysate in the presence and absence of [35S]methionine to compare the structure of [3H]aldosterone-bound and [35S]labeled receptor. In vitro synthesized receptor was able to specifically bind [3H]aldosterone. Unactivated [3H]aldosterone-bound and 60% of unactivated [35S]labeled receptor eluted from DEAE-cellulose with 250 mM salt and had a Rs of 72A. Forty percent of unactivated [35S]labeled receptor eluted from DEAE-cellulose with 100 mM salt and had a Rs of 54A. SDSPAGE showed intact hMR was present in both DEAE-cellulose eluates as three bands between M(r) 110,000-120,000. However, the low salt eluate contained less intact receptor and more lower MW bands. Neither [3H]aldosterone-bound nor [35S]labeled receptor was activated by incubation at 25 degrees C as readily as glucocorticoid receptor studied under identical conditions. Activated [3H]aldosterone-bound receptor eluted from DEAE-cellulose at 100 mM salt and had a Rs of 37A. After activation, 60% of [35S]labeled receptor eluted from DEAE-cellulose with 100 mM salt and had a Rs of 91A. SDS-PAGE of the high and low salt DEAE-cellulose eluates showed that 50% of intact receptor eluted in the low salt peak after activation. These data indicate that: 1. Some in vitro synthesized mineralocorticoid receptor assembles into the heteromeric unactivated form; 2. The remaining intact receptor remains monomeric and unable to bind steroid; 3. Activation causes dissociation of intact receptor from a larger complex; and 4. Activated receptor tends to aggregate.

Aldosterone

The quality assurance committee in a general hospital: its use in improvement of the medical record.

A twice-yearly audit of a sample of medical records from each department of a general hospital was initiated by a quality assurance committee and pursued for 8 years. Missing entries that were considered obligatory for good medical performance of each service were identified, and the results (expressed as percent of missing entries of the total) were communicated in graphic form to the specific departments and the senior staff of the hospital. This approach led to an improvement in the medical records (decrease of missing entries), which may reflect a higher quality of medical care. Thus, a sequential audit of medical records by a quality assurance committee may constitute a simple and effective method of monitoring and improving physicians' knowledge and performance.

Hospitals, District

Photodynamic therapy for the treatment of basal cell carcinoma.

BACKGROUND: Photodynamic therapy is an investigational method for the treatment of a variety of solid tumors. The purpose of this study was to determine the optimum factors and illustrate the effectiveness of photodynamic therapy in the treatment of basal cell carcinomas. This was a prospective study in which patients presenting with primary or recurrent basal cell tumors, particularly but not exclusively widespread tumors or large single tumors, were offered the option of photodynamic therapy in their treatment regimen. RESULTS: Patients were administered 1 mg/kg of a photosensitizer (Photofrin II). Light doses (630 nm) ranged from 72 to 288 J/cm2. A total of 37 patients with 151 sites were treated in this study. A complete response rate of 88% was achieved with one application. Morbidity was low; the most significant side effects were moderate pain and edema. CONCLUSIONS: Photodynamic therapy is a modality that offers localized treatment of primary or recurrent nonmelanoma skin cancer. By applying reciprocal doses of photosensitizer and light, the efficacy of photodynamic therapy in the treatment of skin lesions is demonstrated achieving significant light penetration into tissue with a high complete response rate of the lesions and acceptable normal tissue response.

Basal Cell Carcinoma

[Poststreptococcal reactive arthritis].

Reactive arthritis is defined as arthritis of 1 or more joints, in association with infection at a distant site, but without the infective agent being found in the synovial fluid. Patients with Group A beta-hemolytic streptococcal infection and articular disease, who do not fulfill the modified Jones criteria for diagnosis of acute rheumatic fever, have been classified as having poststreptococcal reactive arthritis. We describe 6 patients seen during the winter of 1991 who had various clinical presentations of poststreptococcal reactive arthritis. This condition is considered by some as a distinct disease, but by others as part of the spectrum of acute rheumatic fever.

Adolescent

Leg muscle scintigraphy with 99Tcm-MIBI in the assessment of peripheral vascular (arterial) disease.

A technique for using 99Tcm-methoxyisobutylisonitrile (MIBI) to evaluate leg muscle perfusion in the assessment of peripheral vascular disease (PVD) is described and evaluated. The uptake of MIBI in muscle groups is quantified and normalized to whole body activity. Eleven patients with PVD undergoing angiography and nine controls were studied. There was a significant difference in MIBI uptake in the calf (P less than 0.000 01) and thigh (P less than 0.0001) between the two groups on exercise. The technique has a sensitivity of 91% and specificity of 94% for the diagnosis of PVD. The technique can also effectively evauate the severity of disease as shown by significant correlations between exercise calf flow and angiographic severity (P less than 0.05) and Doppler ankle/arm pressure measurements (P less than 0.0005). Single photon emission tomography (SPET) of the calves was also performed in five controls and five patients with PVD. Uptake was significantly reduced in all muscle areas in patients with PVD and, amongst those with PVD, uptake was lower in muscle groups by occluded arteries. The potential role of 99Tcm-MIBI in the assessment of PVD and its advantages over other methods of assessment are discussed.

Aged

The hypnotics triazolam and zolpidem have identical metabolic effects throughout the brain: implications for benzodiazepine receptor subtypes.

Using Sokoloff's 2-deoxyglucose autoradiography procedure, the effects of trizolam, a classical benzodiazepine (BZ) hypnotic, were compared to those of zolpidem, which preferentially binds to BZ1 receptor subtypes. Triazolam depressed metabolism in 40 of the more than 60 brain regions evaluated. Zolpidem depressed metabolism in all of these areas, including the spinal cord, an area where the BZ1 receptor subtype is not supposed to exist. Zolpidem and triazolam also depressed metabolism in the molecular layer of the dentate gyrus, an area low in BZ1 receptors. Neither drug affected metabolism in 21 areas, including the regions most specific for the BZ1 subtype (cerebellum, inferior colliculus, globus pallidus, and substantia nigra pars reticularis). It is concluded that: (i) zolpidem and triazolam depress energy metabolism of the same areas of the brain, (ii) zolpidem's effects may not be mediated solely through the BZ1 receptor subtype, and (iii) the BZ2 receptor may be functionally more significant than the BZ1 receptor.

Animals