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Biomedical subjects

J Sinclair

Publications and source records attributed to J Sinclair.

At least 55 records · Page 3Linked to original sources
PubMed1991

Infection and reactivation with cytomegalovirus strains in lung transplant recipients.

Cytomegalovirus pneumonia is a major cause of morbidity and death following lung transplantation (LT) (1). The case fatality rate is highest in the CMV-seronegative recipients (R-) of organs from seropositive donors (D+), which suggests that transmission of CMV may occur with the graft (1), but in seropositive recipients (R+) the comparative importance of reactivation of endogenous virus and reinfection with donor virus is poorly understood.

Cytomegalovirus↗
PubMed1991

Child physical abuse observed. Comparison of families with and without history of child abuse treated in an in-patient family unit.

Twenty-seven families, 14 with a history of child physical abuse and 13 with no such history, were studied over the course of intensive in-patient treatment. The families in the former group differed significantly from those in the latter group in terms of current circumstances and background histories. Families where abuse was admitted benefited significantly more from treatment than families where abuse was suspected but not admitted. The ability of mothers to remember good relationships from childhood and to establish good relationships during treatment was an important prognostic factor for successful treatment.

Adult↗
PubMed1990

Hepatic alcohol dehydrogenase activity in chick hepatocytes towards the major alcohols present in commercial alcoholic beverages: comparison with activities in rat and human liver.

We have compared hepatic alcohol dehydrogenase activities in chick, rat and human liver with the major alcohols in commercial alcoholic beverages. 1. Chick and rat hepatic alcohol dehydrogenase was greater when assayed at a physiological pH in buffer containing chloride ions, as compared with the activity in pyrophosphate buffer at alkaline pH. 2. In contrast to reports of instability of ADH to freezing, we found the enzyme from all three species stable to freezing in 0.25 M sucrose. 3. Rat liver enzymatic activity was unstable in the presence of substrate, where as that of chick and human was not. 4. For all three species, the Km of hepatic ADH for substrate decreased with increasing chain length of alcohols. In both chick and human samples, the Vmax values for the higher chain alcohols were similar to that with ethanol, while in rat samples, ADH activity was dramatically lower with the higher chain alcohols compared to ethanol.

1-Propanol↗
PubMed1990

Pharmacokinetics, biodistribution and dosimetry of 99Tcm(V)DMSA in humans with squamous cell carcinoma.

Technetium-99m (99Tcm)(V) dimercaptosuccinic acid (DMSA) is a new tumour imaging agent which has been used to evaluate squamous carcinoma (SCC) of the head and neck. This study evaluated the pharmacokinetics and biodistribution of 99Tcm(V)DMSA in patients with SCC and calculated the bone mass of a New Zealand White (NZW) rabbit. This data was then used to calculate the effective dose equivalent in man. A total of 16 patients were studied (5 with no tumour, 11 with tumour). 99Tcm(V)DMSA had a fast bi-exponential blood clearance in patients with no tumour (30 and 401 min) and patients with tumour (30 and 387 min) with no significant difference (p greater than 0.05) between the two groups. 99Tcm(V)DMSA had a fast cumulative urine excretion with mean half-times in non-tumour and tumour patients of 183 min and 244 min respectively. There was no significant difference (p greater than 0.05) between these two latter groups. The effective dose equivalent of 99Tcm(V)DMSA in man is 5.1 microSv/MBq.

Aged↗
PubMed1990

c-erbB-2 oncoprotein expression in mammary and extramammary Paget's disease: an immunohistochemical study.

Over-expression of the c-erbB-2 oncogene occurs in a proportion of human adenocarcinomas and in breast carcinoma is associated with poorer prognosis. Sections of formalin-fixed, paraffin-embedded tumour tissue from 22 patients with mammary and extramammary Paget's disease have been stained immunohistochemically using a monoclonal antibody (NCL-CB11) raised against a synthetic peptide from the C-terminal end of the predicted sequence of the c-erbB-2 protein product. All 12 cases of mammary Paget's disease showed membrane staining of intra-epidermal cells, indicating c-erbB-2 over-expression. Sections of underlying ductal breast carcinoma were available in nine cases; all nine tumours were c-erbB-2 positive and in eight the in situ component was of comedo or solid type. There was membrane staining of tumour cells in four of the 10 cases of extramammary Paget's disease; staining intensity was generally weaker than that observed in the cases of mammary disease. The possible implications of these findings for the histogenesis of both mammary and extramammary Paget's disease are discussed.

Breast Neoplasms↗
PubMed1989

Medical staffing in Ontario neonatal intensive care units.

Advances in technology have improved the survival rates of infants of low birth weight. Increasing service commitments together with cutbacks in Canadian training positions have caused concerns about medical staffing in neonatal intensive care units (NICUs) in Ontario. To determine whether an imbalance exists between the supply of medical personnel and the demand for health care services, in July 1985 we surveyed the medical directors, head nurses and staff physicians of nine tertiary level NICUs and the directors of five postgraduate pediatric residency programs. On the basis of current guidelines recommending an ideal neonatologist:patient ratio of 1:6 (assuming an adequate number of support personnel) most of the NICUs were understaffed. Concern about the heavy work pattern and resulting lifestyle implications has made Canadian graduates reluctant to enter this subspecialty. We propose strategies to correct staffing shortages in the context of rapidly increasing workloads resulting from a continuing cutback of pediatric residency positions and restrictions on immigration of foreign trainees.

Health Services Needs and Demand↗
PubMed1989

The clinical features of paediatric meningococcal disease Auckland, 1985-87.

An epidemic of group A meningococcal disease began in Auckland in May 1985. There were 122 paediatric cases of meningococcal disease in the next 25 months including 98 cases due to group A. The commonest clinical symptoms were vomiting, headache and photophobia, while frequent signs included fever, seizures, petechial rash and meningism or a bulging fontanelle. Complications were uncommon and included sterile arthritis and prolonged fever. The majority had disease confirmed by positive blood or cerebrospinal fluid culture. Significantly fewer positive cultures were seen in those treated with antibiotics prior to admission. The overall mortality was 7%. If the acute illness was survived, the only detected long term sequela was sensorineural hearing loss seen in 6%. A vaccine programme has been undertaken to control this epidemic.

Adolescent↗
PubMed1989

Immunochemical detection of different isoenzymes of cytochrome P-450 induced in chick hepatocyte cultures.

This study investigated whether the same cytochrome P-450 (P-450) isoenzymes were inducible in cultures of chick-embryo hepatocytes as in the liver of chicken embryos. We purified two isoenzymes of cytochrome P-450 from the livers of 17-day-old-chick embryos: one of molecular mass approx. 50 kDa induced in vivo by the phenobarbital-like inducer glutethimide, and the second of approx. 57 kDa induced by 3-methylcholanthrene. Rabbit antiserum against the 50 kDa protein inhibited benzphetamine demethylase activity in hepatic microsomes (microsomal fractions) from glutethimide-treated chick embryo. Antiserum to the 57 kDa protein inhibited ethoxyresorufin de-ethylase activity in hepatic microsomes from methylcholanthrene-treated chick embryo. Cultured chick hepatocytes were treated with chemicals known to induce isoenzymes of P-450 in rodent liver. The induced P-450s were quantified spectrophotometrically and characterized by immunoblotting and enzyme assays. From these studies, chemical inducers were classified into three groups: (i) chemicals that induced a P-450 isoenzyme of 50 kDa and increased benzphetamine demethylase activity: glutethimide, phenobarbital, metyrapone, mephenytoin, ethanol, isopentanol, isobutanol, lindane, lysodren; (ii) chemicals that induced a P-450 isoenzyme of 57 kDa and increased ethoxyresorufin de-ethylase activity: 3-methylcholanthrene and 3,3',4,4'-tetrachlorobiphenyl; and (iii) the mono-alpha-substituted 2,3',4,4',5-pentabromobiphenyl, which induced both proteins and both activities. The immunochemical data showed that chick-embryo hepatocytes in culture retain the inducibility of glutethimide- and methylcholanthrene-induced isoenzymes of P-450 that are inducible in the liver of the chicken embryo.

Animals↗
PubMed1989

An outbreak of meningococcal disease in Auckland, New Zealand.

A large epidemic of disease caused by Group A sulfonamide-resistant Neisseria meningitidis has been occurring in Auckland, New Zealand, from June, 1985, and peaking in October, 1985 (spring), and June, 1986 (winter). By the end of 1986 an overall attack rate of 8.3 cases/100,000 total population per year had been calculated. The attack rate in children younger than 15 years was 30.4/100,000/year and the highest rate occurred in children younger than 5 years: all Auckland 68.8/100,000/year; South and Central Auckland 98.7/100,000/year. Seventy-nine percent of cases younger than 15 years of age occurred in 30% of the childhood population. The overall case-fatality ratio was 7% with the highest rate (22%) occurring in male children age 1 to 2 years. An outbreak in an industrialized country of an infectious disease usually seen in developing countries calls for investigation of living conditions and other sociodemographic factors in the population affected. Specific action in the form of a vaccination program particularly targeted to those at risk was planned and implemented before the winter of 1987.

Age Factors↗
PubMed1989

A comparison of high and low fat meals on postprandial esophageal acid exposure.

Fatty foods have been identified as precipitating factors in symptomatic gastroesophageal reflux (GER). A fat meal has also been found to decrease lower esophageal sphincter pressure (LESP) in normal subjects. We used the ambulatory 24-h pH monitor to assess esophageal acid exposure in 10 normal subjects and 10 GER patients following low and high fat meals eaten in two body positions. The meals had nearly identical protein content, volumes, and calories. On successive days, patients ingested one of the meals twice, followed by random assignment to 3 h upright and 3 h recumbent position. Acid exposure for each hour over a 3-h postprandial (PP) period was assessed as the percent time pH less than 4.0. Increased upright acid exposure occurred in normals after the high fat (6.2 +/- 2.1%; mean +/- SE) compared with the low fat meal (1.5 +/- 0.5%; p less than 0.05). GER patients had greater (p less than 0.05) acid exposure than normals in all study periods, but no differences were found between low and high fat meals in either study position. High fat meals induce upright GER in normals, but do not significantly affect the abnormal amount of GER in patients. In addition, progressive increases in acid exposure were found over the 3 postprandial hours in GER patients in a recumbent position. The findings are consistent with prior data showing decreased LESP with a fat meal in normals.

Adult↗
PubMed1988

Human cytomegalovirus-specific cytotoxic T cells. Relative frequency of stage-specific CTL recognizing the 72-kD immediate early protein and glycoprotein B expressed by recombinant vaccinia viruses.

CTL are held to be an important host defense mechanism in persistent herpes-virus infections. We have therefore studied the nature and specificity of human cytomegalovirus (HCMV)-specific CTL in normal persistently infected individuals. This was achieved by using vaccinia recombinants encoding viral genes expressed at different stages of the virus replicative cycle, a structural glycoprotein gB (vac.gB) and the major 72-kD immediate early nonstructural protein (vac.IE) of HCMV, combined with limiting dilution analysis of the CTL response. In two subjects, 43 and 58% of HCMV CTL precursors (CTLp) lysed vac.IE-infected cells, in contrast to less than 6% lysing gB-infected cells. HCMV-specific CTL could also be generated by secondary in vitro stimulation with vac.gB- but not vac.IE-infected autologous fibroblasts. The high frequency of 72-kD IE protein-specific CTL suggests that this is at least a major recognition element for the HCMV-specific CTL response in asymptomatic persistently infected individuals, and CTL with this specificity may be important in maintaining the normal virus/host equilibrium.

Antigens, Viral↗
PubMed1988

Effects of insulin and insulin-like growth factor I on growth of human leukemia cells in serum-free and protein-free medium.

Human myeloid leukemia cells (HL60) and malignant lymphocytes (Namalwa) were grown in protein-free, Fe-supplemented media and used to study growth responses to insulin and insulin-like growth factor 1 (IGF-I). HL60 cells previously grown in serum-free medium containing microgram quantities of insulin showed an 18-fold reduction in cumulative cell production when grown without insulin. However, the same cells showed reduced or absent growth stimulation with 1 to 100 ng/mL insulin or IGF-I for at least four days following insulin deprivation, indicating that culture conditions modified insulin and IGF-I responses. When the same cells were grown in Fe-supplemented, protein-free medium (RPMI-Fe), insulin and IGF-I caused dose-dependent stimulation of HL60 cell growth with half-maximal stimulation at nanogram concentrations. Namalwa cells grown in protein-free medium showed no response to either hormone. Radioligand binding showed the presence of insulin and IGF-I receptors on both HL60 and Namalwa cells grown in RPMI-Fe. HL60 cells grown in fetal bovine serum had higher, and cells grown with microgram quantities of insulin dramatically reduced, insulin binding. Competitive binding studies and cultures with anti-IGF-I receptor antibody showed insulin and IGF-I stimulated growth through their respective specific receptors. Both insulin and IGF-I stimulate growth of some cultured human leukemia cells, but the presence of insulin or IGF-I receptors alone does not predict growth responses. Culture conditions affect both cellular responses and ligand binding by these hormones and must be closely controlled to study growth responses.

Antibodies, Monoclonal↗
PubMed1987

Evidence for cytochrome P450-mediated oxidation of uroporphyrinogen by cell-free liver extracts from chick embryos treated with 3-methylcholanthrene.

Cell-free preparations from liver of chick embryo treated with 3-methylcholanthrene catalyzed oxidation of uroporphyrinogen I in the presence of NADPH and 3,4,3',4'-tetrachlorobiphenyl. Extracts of untreated embryo liver or liver from embryo treated with glutethimide, a phenobarbital-like inducer of cytochrome P450 in this system, did not catalyse the oxidation. Direct involvement of cytochrome P450 was demonstrated by inhibition of the oxidation by CO, piperonyl butoxide and specific antisera to the methylcholanthrene-induced cytochrome P450. 2,4,2',4'-tetrachlorobiphenyl was inactive in the oxidation. These results may explain the role of induced cytochrome P450 in experimental uroporphyria. The oxidation may be useful as a simple assay for reactive O2 species.

Animals↗