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Biomedical subjects

J P Martin

Publications and source records attributed to J P Martin.

At least 19 recordsLinked to original sources

Simulation of special bubble detectors for PICASSO.

The PICASSO project is a cold dark matter (CDM) search experiment relying on the superheated droplet technique. The detectors use superheated freon liquid droplets (active material) dispersed and trapped in a polymerised gel. This detection technique is based on the phase transition of superheated droplets at about room temperature and ambient pressure. The phase transition is induced by nuclear recoils when an atomic nucleus in the droplets interacts with incoming subatomic particles. This includes CDM particles candidate as the neutralino (a yet-to-discover particle predicted in extensions of the standard model of particle physics). Simulations performed to understand the detector response to neutrons and alpha particles are presented along with corresponding data obtained at the Montreal Laboratory.

Computer Simulation↗

Direct dark matter search using large-mass superheated droplet detectors in the PICASSO experiment.

The PICASSO experiment investigates the presence and nature of dark matter in the Universe. The experiment is based on the detection of acoustic signals generated in explosive phase transitions induced by dark matter particles. This technique is an alternative more traditional detection technique like scintillation and ionisation, which are largely employed for dark matter search. One of the main advantages of this technique, besides its sensitivity to very low nuclear recoil energies (few keV), is its excellent background suppression features. A pilot experiment consisting of six superheated droplet detectors (40 g of active mass) is presently taking data at the Sudbury Neutrino Observatory (SNO) at a depth of 2000 m. We discuss the operation, calibration and data acquisition of the experiment and also the ongoing work to increase the sensitivity and the active mass of the detectors.

Cosmic Radiation↗

A multivariate statistical analysis to follow the course of disease after infection of cats with different strains of the feline immunodeficiency virus (FIV).

A descriptive multivariate assay is described which is suitable to analyze results of a biological experiment with small sample size but high qualitative and quantitative complexity of variables. This type of assay allows evaluation of multiple variables observed in the course of an experimental virus infection (e.g. viremia, nucleic acid detection, antibody titers, clinical parameters, anti-microbial treatments or vaccination) in a single graph. In our study, a multiple correspondence analysis (MCA) was used to correlate a total of 145 measurements from each of a dozen of variables measured in five groups of three cats infected by five isolates of feline immunodeficiency virus (FIV). Three groups of virus isolates with distinct virulence were defined and correlation between dynamics of lymphocyte subset counts and viral virulence was established. Comparison between the primary stages of illness and follow-up examinations were of prognostic value and are thus helpful for development and monitoring of therapeutic strategies.

Acute Disease↗

Granulomatous ulcerative colitis: a re-appraisal of the mucosal granuloma in the distinction of Crohn's disease from ulcerative colitis.

AIMS: To determine whether the presence and location of giant cells or granulomas in relation to crypts distinguishes between ulcerative colitis and Crohn's disease. METHODS AND RESULTS: Twenty-nine large bowel mucosal biopsy specimens showing giant cells and/or granulomas in a background more typical of ulcerative colitis than Crohn's disease were collected between 1986 and 1996. Each was subject to detailed independent analysis by three histopathologists. Follow-up of the cases was by examination of all previous and subsequent gastrointestinal surgical or biopsy material and by scrutiny of the clinical notes by a gastroenterologist. On the basis of the accumulated histological data 10 of these 29 cases were accorded the diagnosis of ulcerative colitis. In nine of these 10 cases the clinical diagnosis, where known, was in keeping with this and all nine contained only crypt-associated giant cells and/or granulomas. The tenth case contained a solitary free-standing granuloma and clinically the patient had perianal disease, suggesting that the true diagnosis was Crohn's disease. CONCLUSIONS: Isolated giant cells and well-defined epithelioid granulomas distant from crypts do not, as a rule, occur in ulcerative colitis, and hence their presence in a colonoscopic biopsy showing features of chronic inflammatory bowel disease is a strong pointer towards the diagnosis of Crohn's disease. Crypt-associated giant cells and granulomas can occur in ulcerative colitis and in themselves are unreliable features for the discrimination between Crohn's disease and ulcerative colitis.

Antigens, CD↗

Crystallization and preliminary X-ray analysis of UDP-N-acetylenolpyruvylglucosamine reductase (MurB) from Staphylococcus aureus.

UDP-N-acetylenolpyruvylglucosamine reductase (MurB) is an essential enzyme in the bacterial cell-wall biosynthetic pathway, making it a potential therapeutic target for novel antibiotics. Diffraction-quality crystals of both the native and Se-methionine-expressed MurB from Staphylococcus aureus have been prepared by sitting-drop vapour diffusion from solutions containing polyethylene glycol (PEG) 8000, ammonium sulfate, sodium cacodylate pH 6.5 and dimethyl sulfoxide (DMSO). Crystals belong to the cubic space group I2(1)3, with unit-cell parameters a = b = c = 178.99 A. X-ray data from these crystals were collected at the Advanced Photon Source 17-ID beamline and were used to solve the MurB structure to 2.3 A resolution.

Carbohydrate Dehydrogenases↗

A structural variation for MurB: X-ray crystal structure of Staphylococcus aureus UDP-N-acetylenolpyruvylglucosamine reductase (MurB).

The X-ray crystal structure of the substrate free form of Staphylococcus aureus UDP-N-acetylenolpyruvylglucosamine reductase (MurB) has been solved to 2.3 A resolution with an R-factor of 20.3% and a free R-factor of 22.3%. While the overall fold of the S. aureus enzyme is similar to that of the homologous Escherichia coli MurB X-ray crystal structure, notable distinctions between the S. aureus and E. coli MurB protein structures occur in residues involved in substrate binding. Analysis of available MurB sequences from other bacteria suggest that the S. aureus MurB structure is representative of a distinct structural class of UDP-N-acetylenolpyruvylglucosamine reductases including Bacillus subtilis and Helicobacter pylori that are characterized by a modified mechanism for substrate binding.

Amino Acid Sequence↗

Analysis of anti-neutrophil cytoplasmic antibodies (ANCA): frequency and specificity in a sample of 191 homozygous (PiZZ) alpha1-antitrypsin-deficient subjects.

BACKGROUND: ANCA are autoantibodies directed against polymorphonuclear cell antigens, mainly proteinase 3 (PR3) and myeloperoxidase (MPO), which are implicated in the pathogenesis of small-vessel necrotizing vasculitis. Alpha1-antitrypsin is the main inhibitor of neutral serine proteinase [i.e. human leukocyte elastase (HLE) and PR3] present in PMN alpha-granules (alphaGr). An association first reported by us between PR3 ANCA and the deficient PiZZ phenotype in ANCA-positive systemic vasculitis, now widely confirmed by others, led us to study the incidence and specificity of ANCA among PiZZ subjects. METHODS: We tested a population of 191 PiZZ (273 sera) for ANCA activity versus 272 PiMM matched control subjects using alphaGr or antigen-specific ELISA [PR3, HLE, MPO, lactoferin (LF) and bactericidal/ permeability increasing protein (BPI)]. RESULTS: The incidence of antibodies directed against alphaGr and HLE but not PR3, MPO, LF or BPI was increased in the PiZZ as compared to the PiMM group (Fisher probability respectively P < 0.0001 and P < 0.05). CONCLUSIONS: ANCA not directed against classical antigens (MPO and PR3) may be found in PiZZ patients. However, these patients do not develop systemic vasculitis features. Therefore, alpha1-antitrypsin deficiency is not sufficient to induce ANCA positive vasculitides, and may only act as a second hit amplifying factor.

Adult↗

In vitro activation of feline immunodeficiency virus in ramified microglial cells from asymptomatically infected cats.

Intravenous infection of cats with feline immunodeficiency virus was used as a model system to study activation of virus replication in brain-resident microglial cells in vitro. Virus release by ramified microglial cells isolated from subclinically infected animals was detectable in cell-free tissue culture supernatant only by reverse transcription and nested PCR of gag-specific RNA sequences and not by virion-associated reverse transcriptase activity. In contrast, cocultivation of in vivo-infected microglial cells with mitogen-activated peripheral blood mononuclear cells (PBMC) regularly allows detection of high virus yields in cell-free tissue culture fluid. Besides uptake and multiplication of microglia-derived virus in PBMC, release of virus from microglia is stimulated by cell contact with PBMC. The data suggest that T lymphocytes patrolling the central nervous system could reactivate the semilatent state of lentiviruses in microglial cells in the course of clinically silent central nervous system infection.

Animals↗

The social impact of multiple sclerosis--a study of 305 patients and their relatives.

PURPOSE: to assess the effects of multiple sclerosis (MS) on the patients' ability to fulfil their chosen family and social roles and to examine the impact of the disease on their relatives. METHODS: a population-based survey of all known patients with MS and their relatives in Hampshire County, England, between 1986 and 1989. RESULTS: Seventy-four% of the total study population of 411 completed the study. The patients' mean age was 48.3 years (range 19-82) and the mean disease duration was 15.8 years. About 16% of patients were depressed on a mood rating scale and a similar number also exhibited symptoms of anxiety. The marital status of most patients had not changed since the onset of MS but 53% of those who were employed at the time of diagnosis gave up their jobs and the standards of living of 37% of patients and their families had declined as a direct result of the disease. The ability to continue in gainful employment or to maintain social contacts and leisure activities correlated with the course and severity of the disease and cognitive function. Most carers reported symptoms that clearly related to organic pathologies, anxiety and symptoms of depression. The occurrence of these symptoms was associated with disease severity. The professional career of 57% of relatives was also adversely affected by the patient's illness. CONCLUSIONS: MS has a profound impact on the patients' social roles and their relatives' well-being. In contrast to previous studies, a high divorce/separation rate among patients with MS was not observed. Severe disability and cognitive impairment are predictors of loss of employment, decline in the standards of living and withdrawal from social and leisure activities among patients and are strong indicators of stress among relatives.

Adult↗

In vivo infection of ramified microglia from adult cat central nervous system by feline immunodeficiency virus.

Infection of microglial cells by the human immunodeficiency virus (HIV) is supposed to play an important role in the pathogenesis of AIDS-related central nervous system (CNS) complications. So far, however, experimental data about interactions between HIV and ramified microglia from the adult CNS were only occasionally reported, making it difficult to understand the exact nature of pathogenic events contributing to HIV-encephalopathy. Therefore, we used the animal model of feline immunodeficiency virus (FIV) infection of domestic cats to establish an experimental system which is suitable for studying the relationships between an immunodeficiency virus and the mature ramified microglia of the central nervous system. By means of density gradient centrifugation approximately 95% pure microglial cells could be isolated from adult feline brain that were characterized by their CD45(low) phenotype. Resident microglia extracted from the CNS of experimentally infected cats harbored FIV-specific DNA and cocultivation with mitogen-activated, but uninfected peripheral blood mononuclear cells (PBMC) resulted in recovery of high-titered infectious virus. Double labeling of brain cell monocultures explanted from persistently infected animals for both microglia and FIV markers disclosed less than 1% of viral antigen expressing microglial cells. This suggests that during the subclinical phase of the infection only a small number of brain-resident macrophages are productively infected. However, interaction of FIV-infected microglia and inflammatory lymphocytes may promote viral replication, thus supporting viral spread in brain tissue.

Animals↗

Meckel's diverticulum.

Although Meckel's diverticulum is the most prevalent congenital abnormality of the gastrointestinal tract, it is often difficult to diagnose. It may remain completely asymptomatic, or it may mimic such disorders as Crohn's disease, appendicitis and peptic ulcer disease. Ectopic tissue, found in approximately 50 percent of cases, consists of gastric tissue in 60 to 85 percent of cases and pancreatic tissue in 5 to 16 percent. The diagnosis of Meckel's diverticulum should be considered in patients with unexplained abdominal pain, nausea and vomiting, or intestinal bleeding. Major complications include bleeding, obstruction, intussusception, diverticulitis and perforation. The most useful method of diagnosis is with a technetium-99m pertechnetate scan, which is dependent on uptake of the isotope in heterotopic tissue. Management is by surgical resection.

Female↗

Amylophagia presenting as gestational diabetes.

Amylophagia, or the practice of consuming purified starch, is a particular expression of the more general phenomenon of pica. This compulsive dietary aberration, observed in many pregnant patients worldwide, is common among rural African American women in the southern United States. The effect this practice has on the course of gestational diabetes has not been examined. We report 2 cases of gestational diabetes, refractory to initial dietary management, in which the patients were consuming one-half to 1 box of cornstarch per day. Following cessation of amylophagia, the gestational hyperglycemia spontaneously resolved. Amylophagia is a complex behavioral phenomenon arising from the interplay of biochemical, hematological, psychological, and cultural factors. In some patient populations, it may represent an often overlooked etiologic or exacerbating factor in the condition of gestational diabetes. Family physicians practicing obstetrics should inquire about amylophagia in patients who are at risk for this behavior and in patients who present with gestational hyperglycemia.

Adult↗

Inhaled patient-administered nitrous oxide/oxygen mixture does not impair driving ability when used as analgesia during screening flexible sigmoidoscopy.

BACKGROUND: Entonox (nitrous oxide/oxygen mixture) has an analgesic effect, but its use is currently contraindicated in patients who plan to drive after its administration. We assessed the effect on driving ability of Entonox used as analgesia in patients undergoing screening flexible sigmoidoscopy. METHODS: Forty men and 40 women scheduled for screening flexible sigmoidoscopy who had not driven to the examination site were recruited together with a matched control subject from the same list. Before the examination complex motor skills were assessed in both groups using an adaptive tracking task, previously demonstrated to be the most sensitive test for detecting impairment of driving ability due to drugs. During the examination Entonox analgesia was available to the study group only, and after the screening examination complex motor function was retested on the same computer. RESULTS: Both groups improved their computer score on repeat testing, by 0.53 (range -1.9 to 4.6) in the study group and by 0.44 (range -0.6 to 2.5) in the control group. CONCLUSIONS: These data strongly support the view that Entonox analgesia does not impair driving ability. In the context of screening flexible sigmoidoscopy its use may lead to an increase in compliance.

Ambulatory Surgical Procedures↗

Primary vitrectomy alone for repair of retinal detachments following cataract surgery.

PURPOSE: To report the visual, anatomic, and refractive results of primary vitrectomy alone for the repair of retinal detachments (RD) following cataract surgery. METHODS: Retrospective review of office charts and operative reports of 83 eyes. RESULTS: A minimum of 4 months' follow-up was achieved for 78 pseudophakic or aphakic eyes that underwent primary vitrectomy, internal drainage of subretinal fluid, retinopexy, and intravitreal gas injection for RD repair. Anatomic reattachment was achieved in 93.6% of cases after one procedure and in 96.2% eventually. Median preoperative Snellen acuity was 20/200 and increased to 20/25 at final examination. For the 45 eyes with macula-off detachments, 80% achieved final acuities greater than or equal to 20/40. The average refractive change following surgery was -0.11 diopters. Transient postoperative ocular hypertension was seen in 17.9% and proliferative vitreoretinopathy with recurrent RD in 5.1%. CONCLUSION: Primary pars plana vitrectomy is a highly effective treatment modality for the repair of RD following cataract surgery, and appears to be refractively neutral.

Adult↗

Distribution of alpha(1)-antitrypsin alleles in patients with bronchiectasis.

STUDY OBJECTIVES: Bronchiectasis has been reported in a few patients with homozygous alpha(1)-antitrypsin (AAT) deficiency, but the distribution of AAT alleles among bronchiectatic patients is not known. PATIENTS AND DESIGN: Two hundred two patients, 104 men and 98 women, with a mean age (SD) of 63.7 +/- 15.4 years, had bronchiectasis diagnosed by CT scan alone (n = 178), bronchography with or without CT scan (n = 17), or radiography alone (n = 7). AAT phenotypes (classified according to the protease inhibitor [PI] system) were determined by isoelectric focusing in blood samples obtained from all patients. Bronchiectasis was primary in 121 cases and secondary in 81 patients. Allele and phenotype frequencies were compared retrospectively between bronchiectatic patients and healthy blood donors living in the same geographic area. RESULTS: The PI phenotype frequencies among patients were the following: MM, 81.18%; MS, 11.88%; MZ, 3.46%; IZ, 0.49%; IM, 0.49%; SS, 1.48%; SZ, 0.49%; and ZZ, 0.49%. The allelic frequencies among patients were the following: M, 89.1%; S, 7.67%; Z, 2.72%; and I, 0.49%. There was no difference in the distribution of alleles or phenotypes either between patients and control subjects or between patients with secondary and primary bronchiectasis. A significant difference was found between bronchiectatic patients with and without coexisting emphysema (p = 0.028). This difference was caused by an overrepresentation of PI*Z alleles in bronchiectatic patients with coexisting emphysema. CONCLUSIONS: Our results do not support a physiopathologic implication of the AAT genes in the development of bronchiectasis. We suggest that bronchiectasis may be a consequence of emphysema in PI*Z patients rather than a primary effect.

Adolescent↗

[Diagnostic difficulties of chondrosarcoma of the jaw. Apropos of a case and review of the literature].

Chondrosarcoma is an uncommon malignant mesenchymal tumor characterized by the production of cartilaginous tissue and the absence of production of bone tissue. Maxillary and mandibular localizations are extremely rare and have a poor prognosis. The clinical and radiographic findings are similar to those seen in other tumors of the jaw, often delaying diagnosis and treatment and subsequently jeopardizing prognosis. In the literature, the mean delay from first clinical signs to diagnosis is about 8 months. As in all tumoral diseases, pathology confirms the diagnosis. We report a case of chondrosarcoma of the maxillary bone and review the literature, focusing on the difficulty in establishing the diagnosis, even at the pathology examination. We propose wide surgical excision, which, in agreement with other reports in the literature, is the only therapeutic possibility. We observed no sign of recurrence at 5-year follow-up. Radiotherapy and chemotherapy may be useful in certain cases.

Adult↗

[Proteins of the inter-alpha trypsin inhibitor (ITI) family. A major role in the biology of the extracellular matrix].

A glycoprotein with a high inhibitory activity against trypsin was isolated in 1961 from human plasma and named inter-alpha trypsin inhibitor (ITI). Since then, several other proteins that share antigenic and structural similarities with ITI have been identified and classified as members of the ITI protein family. These glycoproteins built up from different combinations of four polypeptides HC1, HC2, HC3 and bikunin are encoded by four genes H1, H2, H3, L on three chromosomes. Bikunin has two proteinase inhibitor domains and belongs to the Kunitz-type protease inhibitor family; it displays an inhibitory activity against trypsin, leukocyte elastase and plasmin. The heavy chains do not have any protease inhibitory properties but have the capacity to interact in vitro and in vivo with hyaluronic acid. This binding promotes the stability of the extra-cellular matrix. Consequently, the ITI protein family is suspected of playing a key role in the extra-cellular matrix biology. Isolation of free heavy chains in bronchial secretions and the recent emphasis about the bikunin role in tumoral invasion should enhance the interest about ITI protein family in the pathophysiology of chronic bronchopulmonary diseases or lung cancer progression.

Antifibrinolytic Agents↗