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Biomedical subjects

G Howard

Publications and source records attributed to G Howard.

At least 163 records · Page 9Linked to original sources
PubMed1990

Recombinant human prorenin from CHO cells: expression and purification.

The gene for human preprorenin was obtained from total RNA prepared from primary human chorion cells. An expression vector was constructed containing an SV40 early promoter, a human preprorenin cDNA, bovine growth hormone poly-A addition signal, and a dihydrofolate reductase (dhfr) expression cassette. This vector was inserted into the DXB-11 Chinese hamster ovary (CHO) cell line. The recombinant protein was exported by CHO cells into the tissue culture media. At harvest the prorenin levels ranged from approximately 1-5 mg/L. For prorenin isolation the cell culture supernatants were processed by filtration, concentration, dialysis, and batch extraction. Preparative-scale isolation of prorenin was accomplished using blue-dye chromatography and size-exclusion chromatography. The isolated prorenin yielded a single SDS-gel band with Mr approximately 40,000. The proprotein was characterized with respect to N-terminal sequence and N-linked sugar composition. Trypsin-activated renin prepared from the proprotein was characterized with respect to N-terminal sequence and pH-activity profile. Enzyme activity was measured with a newly developed fluorogenic peptide substrate containing the P6-P'3 sequence of human angiotensinogen.

Amino Acid Sequence↗
PubMed1990

Decision rules for the ECG diagnosis of inferior myocardial infarction.

ECG measurements from 341 patients with inferior myocardial infarction (IMI) and 327 normal subjects were used to develop and test decision rules for the ECG diagnosis of IMI. Recursive partitioning provided a simple decision rule with 75% sensitivity and 97% specificity, using Q amplitude and Q duration in a VF, Q duration in III, and T-wave axis in the frontal plane as decision variables. Dropping T-wave axis from the decision rule led to a 10% decrease in sensitivity. Multiple logistic regression provided sensitivities and specificities which were similar to those for recursive partitioning. Both methods outperformed traditional noncontour criteria for IMI.

Adult↗
PubMed1990

Comparative studies of the mutagenicity of urine from smokers and non-smokers on a controlled non-mutagenic diet.

Measuring the mutagenicity of urine is widely viewed as a means of evaluating human exposure to potentially genotoxic materials. Diet and cigarette smoking have both been reported to affect the mutagenicity of human urine, but the relationship between smoking status and the expression of diet-related urinary mutagenicity is unknown. It has been reported that some promutagens are more active in in vitro assays when tested in the presence of urine from smokers than when tested in the presence of urine from non-smokers. We aimed to determine whether the differences in urinary mutagenicity between smokers and non-smokers result from increased urinary mutagenicity from dietary heterocyclic amine mutagens in smokers compared with non-smokers. Groups of smokers and non-smokers (6-12) were given identical diets, previously shown to be low in heterocyclic amines and very low in mutagenicity. The diet consisted exclusively of raw food and of food cooked in boiling water. After a 2-day dietary stabilization period, 24-hour urine samples were collected for three consecutive days. The regimen was repeated in the following week. For comparison, both groups were also placed on a "western" diet, consisting of a variety of foods prepared by several cooking methods, designed to reflect what a typical United States family might consume. Urine was concentrated using XAD-2 resin and then assayed for mutagenic activity in the Ames test. The urine of smokers was significantly more mutagenic than that of non-smokers when on both the raw/boiled and the "western" diets. These results indicate that the increased urinary mutagenicity observed in smokers compared with non-smokers is not due to enhanced mutagenicity of diet-related heterocyclic amine mutagens in the urine of smokers.

Adult↗
PubMed1990

Characteristics of stroke victims associated with early cardiovascular mortality in their children.

We assessed the relationship between characteristics of stroke victims and the risk of early death from coronary or cerebrovascular disease (CCVD) among their children. For each of 55 stroke patients selected from a registry which enrolled patients between 1969 and 1973, an index of their progeny's survival was calculated using the age in 1987 of 197 surviving children, and the age at and cause of death for 55 deceased children. Increased risk of CCVD death within families was significantly related to parental age at the time of first stroke, and with the parental history of diabetes mellitus. No significant relationship was found between the children's risk of CCVD death and the stroke patient/parent's sex, race, history of hypertension or cardiac disease, stroke diagnosis (infarction vs hemorrhage), or severity upon admission. These results suggest that family histories of cerebrovascular disease may impart differential risks, depending upon a family history of diabetes, and perhaps, the ages at which ancestral strokes first occurred.

Adolescent↗
PubMed1990

Regulation of amylase gene expression in diabetic mice is mediated by a cis-acting upstream element close to the pancreas-specific enhancer.

We localized the cis-acting sequences that mediate the regulation of a pancreatic amylase gene, Amy-2.2, in diabetic mice. We constructed three hybrid genes containing sequences from the 5'-flanking region of the amylase gene upstream of the heterologous elastase promoter linked to the CAT structural gene. These constructs were transferred to the germ line of transgenic mice by microinjection of fertilized eggs. The amylase sequences had two effects on expression of the elastase promoter: Basal expression was increased, and expression in diabetic animals was reduced to approximately 2% of basal levels. A 30-bp amylase fragment was sufficient to transfer both of these regulatory functions to the elastase promoter. Sequences within this 30-bp fragment are included in the binding site for the pancreatic nuclear protein PTF1. The close association of the PTF1-binding site and the regulatory functions is consistent with a mechanism based on interference with activation by PTF1 in diabetic pancreas. PTF1-binding activity is not reduced in diabetic pancreas. The data presented here demonstrate that the 5'-flanking region of the pancreatic amylase gene contains a novel insulin-dependent element (IDE) that mediates the loss of expression in diabetic animals.

Amylases↗
PubMed1990

Alcoholism and drug abuse--some legal issues for employers.

Three specific areas of the law concern employers faced with problems of addiction at the workplace. At common law an employer may be guilty of negligence where a person has suffered personal injuries or economic loss as a result of an act of negligence committed in the course of employment by an employee. An example would be an employee with a serious addiction to alcohol or drugs who caused an accident in the company car whilst on company business. Employers may also be guilty of a criminal offence for breach of a statutory duty. One such duty is to have a 'safe system of work'. Other statutory rights guarantee employees a right not to be unfairly dismissed and this includes employees with addiction problems. Lastly, employers must be careful not to break the contract of employment if, for example, an employee with an addiction problem were to be suspended from duty or have his company car withdrawn, even if this was a temporary measure only.

Accidents, Traffic↗
PubMed1990

Some legal issues relating to passive smoking at the workplace.

This paper will discuss some of the current legal issues concerning passive smoking at the workplace. Employers who introduce 'No Smoking' policies must take care in the manner in which they introduce any rules and the extent to which the new rules affect those employees who have always been permitted to smoke at work. Changing the rules in an arbitrary fashion may give rise to claims for breach of contract. Smokers may also sue for constructive dismissal should the new rules be imposed in an unreasonable manner. But employers who have followed a fair procedure may have the right to discipline or finally dismiss any smoker who refuses to accept the new rules.

Employee Discipline↗
PubMed1990

Community hospital-based stroke programs in North Carolina, Oregon, and New York. IV. Stroke diagnosis and its relation to demographics, risk factors, and clinical status after stroke.

The use of diagnostic tests, the accuracy of stroke type diagnosis, and their relationship to outcome are important from the standpoint of patient management and health care costs. To address this issue, we examined the differences between stroke types in terms of demographics, risk factors, diagnostic tests, and clinical outcome in the 4,129 patients who comprise the Community Hospital-Based Stroke Program. Previous transient ischemic attacks were equally frequent among patients with embolic and those with thrombotic stroke. For all stroke types, previous stroke was as frequent as previous transient ischemic attacks. Hypertension and cardiac disease were the most common risk factors, but 10% of all stroke patients had no recognized risk factors. Intracerebral hemorrhage was most often associated with death (45%). There was a strong direct relation between in-hospital mortality and a decreased level of consciousness at admission. Overall, 30% of patients did not receive a specific stroke type diagnosis; these patients were elderly, usually nonwhite, and often had an altered level of consciousness at admission but had a risk factor profile similar to that of patients who received a specific stroke type diagnosis. In summary, our findings suggest the continued need for physician education about and refinement of stroke type diagnosis.

Aged↗