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Biomedical subjects

C Berry

Publications and source records attributed to C Berry.

At least 91 records · Page 5Linked to original sources

Nine novel L1 CAM mutations in families with X-linked hydrocephalus.

Mutations in the gene for neural cell adhesion molecule L1 are responsible for the highly variable phenotype found in families with X-linked hydrocephalus, MASA syndrome, and spastic paraplegia type I. To date, 32 different mutations have been observed, the majority being unique to individual families. Here, we report nine novel mutations in L1 in 10 X-linked hydrocephalus families. Four mutations truncate the L1 protein and eliminate cell surface expression, and two would produce abnormal L1 through alteration of RNA processing. A further two of these mutations are small in-frame deletions that have occurred through a mechanism involving tandem repeated sequences. Together with a single missense mutation, these latter examples contribute to the growing number of existing mutations that affect short regions of the L1 protein that may have particular functional significance.

Amino Acid Sequence↗

Retinoic acid, neoplasia, differentiation and development.

Retinoic acid has pronounced effects on cultures of neoplastic cells. These have attracted the attention of pathologists, but it is important to note that much of the critical data about retinoic acid has been obtained from the current extension of our knowledge in the field of development. Some of these changes are reviewed here.

Animals↗

Intraocular pressure and aqueous humor dynamics in patients with AIDS treated with intravitreal cidofovir (HPMPC) for cytomegalovirus retinitis.

PURPOSE: To evaluate the decrease in intraocular pressure associated with cidofovir (1-[(S)-3-hydroxy-2-(phosphonomethoxy)propyl]cytosine dihydrate; HPMPC) intravitreal injections. METHODS: We followed up 97 eyes of 63 patients with acquired immunodeficiency syndrome (AIDS) who had cytomegalovirus retinitis and had been treated with up to nine 20-microgram intravitreal cidofovir injections. Measurements were taken at baseline, between 2 and 3 weeks, and at 5 to 6 weeks after injections. Anterior chamber fluorophotometry was studied in seven eyes (four patients) before and after injections. Ciliary body anatomy was evaluated in two patients. RESULTS: After the first intravitreal injection, mean intraocular pressure was 2.2 mm Hg lower than that at baseline at 2 to 3 weeks (P < .001) and 1.3 mm Hg lower than at baseline at 5 to 6 weeks (P = .0025). After the second injection, mean pressure was 2.6 mm Hg lower at 2 to 3 weeks (P = .0013) and 1.5 mm Hg lower at 5 to 6 weeks (P = .043). After subsequent injections, however, the decrease was less than 1 mm Hg, suggesting that a plateau had been reached. Pressure in eyes with anterior uveitis after the first injection was lower than that in eyes without anterior uveitis (P < .0001). The mean rate of aqueous flow decreased from 2.8 to 1.9 microliters per minute 2 to 4 weeks after injection (P < .015). Ultrasound biomicroscopy disclosed that severe hypotony after cidofovir injections is associated with ciliary body atrophy. CONCLUSIONS: Intraocular pressure decreases after the initial 20-microgram cidofovir intravitreal injection. However, eyes stabilize (pressure plateaus) after three injections. Effects on the ciliary body are the main cause of the decrease after cidofovir injections.

Acquired Immunodeficiency Syndrome↗

Lipoprotein subfraction concentrations in preeclampsia: pathogenic parallels to atherosclerosis.

OBJECTIVE: To determine whether large triglyceride-rich lipoproteins, very-low-density lipoprotein1 (VLDL1), and small, dense low-density lipoprotein (LDL-III), are significantly increased in women with preeclampsia compared with concentrations seen in normal pregnancy. METHODS: Plasma concentrations of very-low-density and low-density lipoprotein subfractions and pre-heparin hepatic lipase activity were measured in eight women with preeclampsia and in eight healthy pregnant controls matched for age, gestational age, and weight. RESULTS: Women with preeclampsia exhibited higher median plasma triglyceride concentrations (3.68 versus 1.93 mmol/L, P = .004) compared with controls. This was reflected in an almost threefold increase in median VLDL1 (184 versus 68 mg/dL, P = .002) and a twofold increase in very-low-density lipoprotein2 (VLDL2) (146 versus 76 mg/dL, P = .014), whereas total plasma cholesterol, intermediate-density lipoprotein, and total LDL concentration were the same in subjects and controls. Furthermore, women with preeclampsia demonstrated significantly lower concentrations of the large, buoyant LDL subfractions, LDL-I and LDL-II, and markedly elevated median plasma concentrations of small, dense LDL, LDL-III (170 versus 55 mg/dL, P = .024). High-density lipoprotein-cholesterol concentration also was significantly lower (P = .021), and pre-heparin hepatic lipase activity was significantly elevated (29 versus 18 mumol fatty acids/mL/hour, P = .041) in the preeclamptic group. The concentration of small, dense LDL correlated positively with plasma triglyceride concentration (r2 = 0.504, P = .002). CONCLUSION: Women with preeclampsia exhibit markedly elevated concentrations of triglyceride-rich lipoproteins in the circulation. These particles are potential contributors to endothelial dysfunction and the expression of preeclampsia, both directly and, indirectly, through the generation of small, dense LDL.

Adult↗

Memory and CD8+ are the predominant bovine bronchoalveolar lymphocyte phenotypes.

Bovine lymphocytes obtained by bronchoalveolar lavage (BAL) of healthy calves were simultaneously analyzed and compared to peripheral blood lymphocytes using monoclonal antibodies specific for bovine leukocyte differentiation antigens. Phenotypic differences were observed between bronchoalveolar and peripheral blood T-lymphocyte subpopulations, demonstrating selective lymphocyte migration to the bovine lung. The bronchoalveolar and peripheral blood T-lymphocyte populations, defined by expression of CD2, were similar, but bronchoalveolar T lymphocytes were predominately CD8+ while peripheral blood T cells were predominately CD4+. In addition, memory lymphocytes, characterized by low expression of CD45R and activated lymphocytes (CD25+), were found in significantly higher proportions in the bronchoalveolar compartment. The proportion of gammadelta T lymphocytes was, however, significantly higher in peripheral blood. B cells were observed in similar proportions in the bronchoalveolar compartment and peripheral blood.

Animals↗

Iodinated methacrylate copolymers as X-ray opaque denture base acrylics.

OBJECTIVES: The purpose of this study was to evaluate novel iodinated methacrylate copolymers as X-ray opaque denture base resins. METHODS: The synthesis of specific monomers and suspension copolymerization with methyl methacrylate to produce copolymer beads. The resulting beads were processed in an identical manner to standard PMMA to produce test-pieces for mechanical testing. RESULTS: Samples prepared from beads containing 25 wt% of the iodinated copolymer exhibited an X-ray opacity equivalent to that exhibited by a similar thickness of aluminium. Furthermore, the appearance and mechanical properties were comparable to standard PMMA, while thermal stability proved superior. CONCLUSION: These novel iodinated methacrylate monomers show promise not only as polymerizable additives to methyl methacrylate to produce an X-ray opaque denture base but also as thermally stable copolymerizable additives to other applications where X-ray opacity would be advantageous.

Contrast Media↗

Liver imaging in the cat.

This article presents the most common indications and illustrates the use of radiography, ultrasonography, and scintography in the diagnosis of hepatic disorders in cats.

Animals↗

Phase I trial and pharmacokinetics of the tubulin inhibitor 1069C85--a synthetic agent binding at the colchicine site designed to overcome multidrug resistance.

The orally administered tubulin-binding agent 1069C85 was developed with the hope of overcoming the multidrug resistance associated with existing anti-tubulin agents, such as the vinca alkaloids. A phase I study was performed using a single oral dose every 3 weeks, administered as a suspension reconstituted in 0.1% Tween 80 and 0.9% saline. The starting dose was 2.8 mg m-2, and dose doubling was permitted until the area under curve (AUC) was > or = 40% of that at the mouse LD10; thereafter, a modified Fibonacci scheme was used. The formulation proved to be unsatisfactory, resulting in inconsistent absorption. The terminal elimination half-life was prolonged (range 18-73.5 h). Sporadic central neurotoxicity was observed, which was grade 3 in one patient treated at 200 mg m-2. A revised formulation with micronized drug was more easily suspended and appeared to increase the bioavailability by a factor of 2-4. Severe central neurotoxicity, up to grade 4, was then observed at doses of 50-100 mg m-2. Unfortunately, toxicity was not predictable and one patient, with a previous history of partial intestinal obstruction, treated at 50 mg m-2, cleared the drug very slowly, possibly because of prolonged, delayed absorption. This patient died from pancytopenia and severe gastrointestinal damage. It was concluded that such unpredictable behaviour would be incompatible with safe evaluation in phase II studies; the trial was closed and further clinical development abandoned.

Administration, Oral↗

Impact of the American Stop Smoking Intervention Study on cigarette consumption.

OBJECTIVE: To obtain an early estimate of the effectiveness of the American Stop Smoking Intervention Study (ASSIST). DESIGN, SETTING, AND PARTICIPANTS: Seventeen American states funded through ASSIST are compared with 32 others regarding per capita cigarette consumption from 1989 to 1995. California, which already had an extensive tobacco control programme, was omitted. ASSIST states were selected competitively (not randomly) based on their proposals' merit, state smoking prevalence, and geographical distribution. INTERVENTIONS: Comprehensive tobacco control programmes, emphasising policy interventions, were implemented in the ASSIST states beginning in 1993. MAIN OUTCOME MEASURES: Trends in aggregated per capita cigarette consumption and inflation-adjusted average price/pack of cigarettes in the intervention states were compared. Percentage change in per capita consumption is also compared with percentage change in inflation-adjusted cigarette price by state in each group from 1992 to 1994. RESULTS: Per capita consumption and inflation-adjusted cigarette price were nearly identical in both groups of states before 1993, when full funding for the ASSIST interventions began. However, by 1996 smokers in the intervention states were consuming about 7% less cigarettes per capita (P<0.05, beginning in 1994), and in 1994 the average price was over $0.12/pack higher in the intervention states. All but three states (all intervention) showed decreases in cigarette price. Nonetheless, 76% of the intervention and 55% of the comparison states showed some decrease in consumption despite decreases in price. The relationship between changes in price and consumption was considerably diminished in the intervention group. CONCLUSIONS: These interim results suggest that the ASSIST programme is associated with a substantial difference in tobacco consumption in a third of the United States, and that increased price from taxation may not be the only programme influence.

Health Promotion↗

Phase I and pharmacokinetic study of an oral platinum complex given daily for 5 days in patients with cancer.

PURPOSE: We aimed to determine the maximum-tolerated dose (MTD) clinical toxicities, pharmacokinetics, and pharmacodynamics of oral JM216 given once daily for 5 days to cancer patients. PATIENTS AND METHODS: Patients who fulfilled standard phase I trial criteria were enrolled. Oral JM216 was given at doses based on patient body-surface area, on an empty stomach, once daily for 5 consecutive days, as 10-, 50-, and 200-mg hard gelatin capsules and with oral antiemetics. The pharmacokinetics of platinum were studied on days 1 and 5 of the first treatment course using atomic absorption spectrophotometry (AAS). RESULTS: Thirty-two patients received 94 courses of oral JM216 at doses that ranged from 30 to 140 mg/m2 body-surface area for 5 consecutive days. The MTD was 140 mg/m2/d. The dose-limiting toxicities were thrombocytopenia and neutropenia. Hematotoxicity was reversible (nadir, 17 to 21 days; recovery, 28 days), noncumulative, and dependent on the dose and history of previous therapy. There were two instances of neutropenic sepsis. Two-thirds of patients experienced mild nausea, vomiting, or diarrhea. There was no ototoxicity, neurotoxicity, nephrotoxicity, or objective tumor responses. There was a significant correlation between JM216 dose and the day 1 and 5 plasma ultrafiltrate area under the concentration-time curve (AUC; r = .78), which indicates linear pharmacokinetics. There was considerable intersubject pharmacokinetic and pharmacodynamic variability, but a significant sigmoidal relationship between the plasma ultrafiltrate AUC and severity of thrombocytopenia (R2 = .83). CONCLUSION: We recommend JM216 doses of 100 and 120 mg/m2/d x 5 for previously treated and untreated patients, respectively, for phase II trials.

Administration, Oral↗

Polymerase chain reaction detection of cytomegalovirus and human immunodeficiency virus-1 in the retina of patients with acquired immune deficiency syndrome with and without cotton-wool spots.

PURPOSE: The authors determine the association, if any, between detection of human cytomegalovirus (CMV) and human immunodeficiency virus (HIV) nucleic acids and retinal lesions in patients with acquired immune deficiency syndrome. METHODS: Postmortem eyes were examined with a dissecting microscope and light microscopy. Retinal cotton-wool spots (CWS) were removed using a clean touch punch biopsy technique. Equivalent amounts of retinal tissue from the posterior pole of the retina not affected by CWS and from the retinal periphery also were studied. Polymerase chain reaction (PCR) detection of retinal cellular DNA (GA3PD gene), human CMV DNA (major immediate early gene), and HIV (gag gene) was performed using ethidium bromide and liquid hybridization detection. RESULTS: Ninety percent of CWS were positive for CMV DNA versus 22% of peripheral retinal biopsies (P < 0.025). Liquid hybridization showed similar results. Analysis of lesions in which results of both tests were positive (ethidium and liquid hybridization) versus lesions in which results of either test were negative also showed a strong association between CWS and CMV, but not HIV nucleic acids (P < 0.02). Studies of HIV showed no association between retinal CWS lesions and HIV nucleic acid; with liquid hybridization HIV, RNA was detected equally at low levels in all areas. CONCLUSION: There is a statistically significant association between the presence of human CMV nucleic acids and retinal CWS detected by PCR. There is a low level presence of HIV in the retinal tissue studied that is only detectable using liquid hybridization techniques and is not associated with a particular area or lesions in the retina; this may represent detection of HIV in blood. The presence of CMV in areas of retinal CWS may have implications for their pathogenesis, but further study is necessary because other explanations are possible.

AIDS-Related Opportunistic Infections↗