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Biomedical subjects

B A Brennan

Publications and source records attributed to B A Brennan.

12 recordsLinked to original sources
PubMed2000

Pancreatic vasoactive intestinal polypeptide-oma as a cause of secretory diarrhoea.

A 42-year-old woman presented with a 4-year history of worsening diarrhoea that was watery, profuse and confirmed to be secretory in nature. She had tested positive for phenolphthalein on urinary laxative screening but continued to deny laxative usage. Her vasoactive intestinal polypeptide (VIP) level was subsequently found to be markedly elevated. Despite a normal abdominal ultrasound, a computed tomography scan revealed a 5-cm pancreatic tail mass. Octreotide scanning was used to exclude metastatic disease and she went on to have surgical removal of a localized pancreatic vasoactive intestinal polypeptide-oma which resulted in the complete resolution of her diarrhoea.

Adult↗
PubMed1999

Oval cell numbers in human chronic liver diseases are directly related to disease severity.

The risk of developing hepatocellular carcinoma is significantly increased in patients with genetic hemochromatosis, alcoholic liver disease, or chronic hepatitis C infection. The precise mechanisms underlying the development of hepatocellular carcinoma in these conditions are not well understood. Stem cells within the liver, termed oval cells, are involved in the pathogenesis of hepatocellular carcinoma in animal models and may be important in the development of hepatocellular carcinoma in human chronic liver diseases. The aims of this study were to determine whether oval cells could be detected in the liver of patients with genetic hemochromatosis, alcoholic liver disease, or chronic hepatitis C, and whether there is a relationship between the severity of the liver disease and the number of oval cells. Oval cells were detected using histology and immunohistochemistry in liver biopsies from patients with genetic hemochromatosis, alcoholic liver disease, or chronic hepatitis C. Oval cells were not observed in normal liver controls. Oval cell numbers increased significantly with the progression of disease severity from mild to severe in each of the diseases studied. We conclude that oval cells are frequently found in subjects with genetic hemochromatosis, alcoholic liver disease, or chronic hepatitis C. There is an association between severity of liver disease and increase in the number of oval cells consistent with the hypothesis that oval cell proliferation is associated with increased risk for development of hepatocellular carcinoma in chronic liver disease.

Cell Count↗
PubMed1997

Clinical and endoscopic predictors of histological oesophagitis in infants.

OBJECTIVE: To define the earliest age at which histological changes can be used to diagnose oesophagitis and to determine the relationships between clinical, endoscopic and histological features of oesophagitis in infants. METHODOLOGY: The case records and biopsies of 113 infants aged 2-18 months with clinically significant gastro-oesophageal reflux (GOR), undergoing oesophagoscopy between 1978 and 1994 were retrospectively reviewed. The biopsies were independently evaluated and graded by two pathologists. RESULTS: Forty-five cases (40%) had histological oesophagitis but only 16 (14%) had abnormal endoscopic findings (excluding erythema). Endoscopy was found to be highly specific (93%) for histological oesophagitis but lacked sensitivity (25%). Irritability was inversely related to the presence of endoscopic abnormalities, and there was poor correlation between symptoms and histological changes with only haematemesis showing a statistically significant association with histological abnormalities (P = 0.033). Intraepithelial lymphocytes were the earliest of the histological features noted and were present before 4 months of age. The numbers of intraepithelial eosinophils and lymphocytes and the presence of papillary elongation all increased with age. CONCLUSIONS: The presence of oesophagitis is difficult to predict on the basis of symptoms. The presence of intraepithelial lymphocytes is the earliest histological change to be seen in infants with GOR, and can develop before 4 months of age. Oesophagoscopy without biopsy is unreliable in the diagnosis of oesophagitis in infants.

Endoscopy↗
PubMed1996

Resonance Raman spectroscopy of nitrile hydratase, a novel iron-sulfur enzyme.

Resonance Raman spectra of Rhodococcus sp. R312 (formerly Brevibacterium sp. R312) nitrile hydratase, a novel non-heme iron enzyme, have a large number of peaks in the 300-500 cm-1 region; observation of shifts in these peaks after labeling with 34S shows that they arise from cysteine coordinated to the ferric ion in the protein. The rich Raman spectra result from coupling of the Fe-S stretch with cysteine side chain deformation modes; the observation of 15N isotope shifts in most of these peaks suggests participation of N-donor metal ligands and peptide backbone amide nitrogens in these modes as well. The aggregate 34S isotope shift is too large to result from a single cysteine ligand, consistent with the analysis of EXAFS data that shows two or three S-donor ligands [Scarrow et al. (1996) Biochemistry 35, 10078-10088]. Widespread 2H isotope shifts seen after exchange of the protein into 2H2O suggest the presence of hydrogen bonds to the coordinated cysteine sulfurs. Comparison of the resonance Raman spectra of nitrile hydratase prepared at pH 7.3 and 9.0 shows a shift of intensity into the higher-energy peaks in the spectra of the latter sample. This is interpreted as resulting from an increase in Fe-S bond strength at the higher pH and is supported by observation of a small decrease in Fe-S bond length in the EXAFS analysis [Scarrow et al. (1996) Biochemistry 35, 10078-10088]. Such a decrease in Fe-S bond length is also consistent with pH dependent changes in EPR spectra and could reflect the loss of one or more hydrogen bonds to sulfur ligands.

Brevibacterium↗
PubMed1996

X-ray spectroscopy of nitrile hydratase at pH 7 and 9.

The iron K-edge X-ray absorption spectrum of Rhodococcus sp. R312 (formerly Brevibacterium sp. R312) nitrile hydratase in frozen solutions at pH 7 and 9 has been analyzed to determine details of the iron coordination. EXAFS analysis implies two or three sulfur ligands per iron and overall six coordination; together with previous EPR and ENDOR results, this implies an N3S2O ligation sphere. The bond lengths from EXAFS analysis [rav(Fe-S) = 2.21 A at pH 7.3; rav(Fe-N/O) = 1.99 A] support cis coordination of two cysteine ligands and conclusively rule out nitric oxide coordination to the iron, a possibility proposed on the basis of an FTIR difference experiment [Noguchi, T., Honda, J., Nagamune, T., Sasabe, H., Inoue, Y., & Endo, I. (1995) FEBS Lett. 358, 9-12]. The higher-frequency EXAFS can be simulated well by inclusion of multiple scattering from two or three imidazole ligands; the fit to the data is improved if first-sphere multiple scattering pathways are also included. A slight shortening (by 0.02 +/- 0.01 A) of one or both Fe-S bonds when the pH is raised from 7.3 to 9.0 is consistent with shifts observed in the Raman spectrum [Brennan et al. (1996) Biochemistry 35, 10068-10077].

Absorptiometry, Photon↗
PubMed1996

Parotid lipomatosis.

A case of parotid lipomatosis is reported, and the literature is reviewed. This rare condition presents as a slow growing parotid mass, which may be diagnosed preoperatively using computed tomography or magnetic resonance imaging. Long-term clinical follow-up is important because apparently complete surgical excision may be complicated by recurrence.

Child, Preschool↗
PubMed1995

Structure and kinetics of formation of catechol complexes of ferric soybean lipoxygenase-1.

Ferric soybean lipoxygenase forms stable complexes with 4-substituted catechols. The structure of the complex between the enzyme and 3,4-dihydroxybenzonitrile has been studied by resonance Raman, electron paramagnetic resonance, visible, and X-ray spectroscopies. It is a bidentate iron-catecholate complex with at least one water ligand. The kinetics of formation of complexes between lipoxygenase and 3,4-dihydroxybenzonitrile and 3,4-dihydroxyacetophenone have been studied by stopped-flow spectroscopy. The data are consistent with two kinetically distinct, reversible steps. The pH dependence of the first step suggests that the substrate for the reaction is the catechol monoanion. When these results are combined, plausible mechanisms for the complexation reaction are suggested.

Catechols↗
PubMed1992

Purification and characterization of the blue-green rat phaeochromocytoma (PC12) tyrosine hydroxylase with a dopamine-Fe(III) complex. Reversal of the endogenous feedback inhibition by phosphorylation of serine-40.

Tyrosine hydroxylase (TH) was purified from tumours of rat phaeochromocytoma (PC12) cells by a three-step purification procedure giving 30 mg of pure enzyme in 3 days. The enzyme sedimented with an S(eo),w value of 9.2 S and revealed an apparent subunit molecular mass of 62 kDa with a minor 60 kDa component. Two-dimensional gel isoelectric focusing/electrophoresis and tryptic digestion revealed that the heterogeneity could be accounted for by limited proteolysis of the 62 kDa component and the presence of covalently bound phosphate. The enzyme had a strong blue-green colour (epsilon 700 = 3.1 +/- 0.2 mM-iron-1.cm-1). The resonance Raman spectrum obtained with lambda excitation = 605 nm revealed the presence of an Fe(III)-catecholamine complex in the isolate enzyme, similar to that observed in the bovine adrenal enzyme [Andersson, Cox, Que, Flatmark & Haavik (1988) J. Biol. Chem. 263, 18621-18626]. In the rat PC12 enzyme, all of the iron present (0.53 +/- 0.03 atom per subunit) seems to be chelated by the feedback inhibitors (0.49 +/- 0.05 mol of dopamine and 0.10 +/- 0.03 mol of noradrenaline per mol of subunit). The e.p.r. spectra at 3.6 K show g-values at 7.0, 5.2 and 1.9 as observed for other catecholate-complexed enzymes. After phosphorylation of serine-40 and addition of L-tyrosine a new rhombic (magnitude of E/D = 0.33) e.p.r. species could be observed. Phosphorylation of serine-40 by cyclic AMP-dependent protein kinase increased the catalytic activity; depending on assay conditions, up to 80-110-fold activation could be observed when measured at high TH (i.e. high endogenous catecholamine) concentration.

Adrenal Gland Neoplasms↗
PubMed1986

Time trends in prevalence of cervical cytological abnormality in women attending a sexually transmitted diseases clinic and their relationship to trends in sexual activity and specific infections.

Trends in prevalence of cytological evidence of cervical intraepithelial neoplasia (CIN) and cervical infection with human papilloma virus (HPV), as indicated by HPV infection and dyskeratosis, were studied in 2,992 new attenders at a sexually transmitted diseases (STD) clinic between 1978 and 1982. Crude prevalence of CIN increased from 1.3% to 4.3% (P less than 0.001) and crude prevalence of HPV infection increased from 2.8% to 9.3% (P less than 0.001). Age adjustment had little effect on these trends. Review, in 1984-85, of samples of smears taken in 1978 and 1982 showed that recognition of koilocytosis by the laboratory had increased substantially over time while a tendency had developed to downgrade nuclear changes in the presence of koilocytosis. Correction of the 1978 and 1982 smear results to the 1984-85 classifications suggested that prevalence of koilocytosis had increased little (from 13.4% to 16.1%, P = 0.20) while there had been a substantial real increase in CIN (0.8% to 2.4%, P less than 0.001). To try to explain the trend in CIN, other characteristics of a sample of attenders at the STD clinic were studied. There were no appreciable trends in prevalence of past STD, number of sexual partners in the last 3 months, method of contraception, genital warts and culture of N. gonorrhoea, T. vaginalis, C. albicans and Chlamydia sp. from the vagina. There was an increase in the proportions in socioeconomic group I, as classified by postcode of residence (17.0% to 26.9%, P = 0.04), referred as contacts rather than with symptoms (24.0% to 41.6%, P less than 0.001), with a clinical diagnosis of genital herpes (5.0% to 8.6%, P = 0.08) and with herpes virus cultured from the cervix (2.1% to 6.3%, P = 0.03). The trend in prevalence of herpes virus infection was not explained by the other trends. It may explain the trend in prevalence of CIN.

Age Factors↗
PubMed1978

Midwifery, 1977.

On January 1, 1974, an autonomous midwifery service was formed at Roosevelt Hospital in New York City to provide an obstetric service to "private" patients. While the autonomy was complete, physician consultation and participation provided by the "full-time or senior resident" staff were always available. We are now aware that this plan as opposed to any other, provided the ingredient of consumer-desired empathy of the midwife coupled with instant obstetric expertise that assured every patient the availability of modern obstetric practice. Four hundred and fifty-four patients cared for by midwives were compared to a random sample of 500 patients cared for by attending obstetricians. A striking similarity in the two groups was evident. Certain items, such as operative deliveries, were higher in the private patient group. The midwifery group had a low incidence of complications, but the incidence of acute complications made it apparent that an operating room suite must be immediately available. It is eminently clear that a low-risk group can be identified but there is no possible way to identify a "no risk" population.

Adolescent↗