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Biomedical subjects

J Harris

Publications and source records attributed to J Harris.

At least 181 records · Page 10Linked to original sources

Serum neopterin in chronic beryllium disease.

We evaluated serum neopterin as a biomarker of chronic beryllium disease (CBD), for use in conjunction with the beryllium lymphocyte proliferation test (BeLPT) in workplace screening. Serum neopterin levels were determined by radioimmunoassay, and we compared levels in three groups: CBD (n = 86), beryllium sensitized (BeS) (n = 22), and normal (Nor) (n = 20). Those in the diseased group underwent pulmonary function tests, bronchoalveolar lavage (BAL), and maximal exercise testing. We correlated neopterin levels with results of these clinical parameters of disease severity. To evaluate the optimum sensitivity, specificity, and neopterin cut-off value, receiver operator characteristic (ROC) curves were generated. The median serum neopterin level in CBD was significantly higher than in BeS or in Nor [median 1.45, 25th, 75th percentiles (1.00, 2.7) ng/ml, 0.82 (0.67, 1.16) ng/ml, and 0.92 (0.86, 1.16) ng/ml, respectively] (P < 0.05). In CBD, we observed statistically significant associations between neopterin and measures of gas exchange and BAL cellularity. Using a neopterin value of 1.27 ng/ml, test specificity is 88%. In those workers with an abnormal BeLPT, serum neopterin has high positive predictive value (92%), and can identify disease, helping to distinguish it from BeS without the risks of biopsy.

Adult↗

Glucosephosphate isomerase (GPI) deficiency mutations associated with hereditary nonspherocytic hemolytic anemia (HNSHA).

Five unrelated patients with hereditary glucosephosphate isomerase (GPI) deficiency resulting in nonspherocytic hemolytic anemia were studied. Three new mutations were found in the coding region of the GPI gene: two patients were heterozygous for 223 A-->G (R75G) and 898 G-->C(R300P), respectively and one was homozygous for 1415G-->A(R472H). Surprisingly, 2 previously reported mutations, 286 C-->T and 1039 C-->T, were found in 2 and 3 patients respectively. Until now only 4 of 18 GPI mutations had been found more than once in unrelated patients and these 4 in only 2 patients each. Eleven of the 20 known point mutations have occurred at CpG "hot spots" and the 286 C-->T and 1039 C-->T are among these. The 489 G/A polymorphism in the GPI coding region was used to demonstrate unequivocally that the 1039 C-->T mutation occurred in both haplotypes and therefore probably originated more than once. Because no common GPI mutation has been found we suggest that heterozygosity for GPI confers little if any selective advantage.

Adult↗

Irrelevant peripheral visual stimuli impair manual reaction times in Parkinson's disease.

In three experiments, the effects of irrelevant visual information on the time to initiate and to complete a simple movement of the hand in response to a visual signal were studied in patients with a diagnosis of Parkinson's disease, and in age-matched normal controls. Subjects gazed at the centre of a TV monitor and were instructed to move their preferred hand from one metal plate to another as soon as a blue disc appeared in the centre of the screen. This control condition was compared with other conditions in which the surrounding area of the screen was simultaneously filled with fields of irrelevant discs, which in Experiment 1 were either stationary, or streamed out from or in towards the centre of the screen. Reaction times, but not movement times, were significantly slowed in the patients (but not the controls) by the irrelevant disc fields. When the irrelevant dots were continuously present (between as well as within trials--Experiment 2), they had no effect on RT. When they were present between trials, but turned off as the movement signal was turned on, RT was again slowed in patients. The results are discussed in relation to the akinesia ("freezing") experienced by some patients in confined spaces (such as doorways), and to possible abnormalities of visual cortical and striato-nigro-collicular activity.

Analysis of Variance↗

Conditioned fear to context is associated with increased Fos expression in the caudal ventrolateral region of the midbrain periaqueductal gray.

Immunohistochemical detection of Fos was used to determine which regions of the periaqueductal gray are activated during conditioned fear to a context in the rat. More specifically, the aim of the study was to test the role of its lateral and ventrolateral columns in freezing behaviour during fear. Conditioned fear was evoked by re-exposing rats to the same footshock chamber in which they had received footshocks 4 h earlier. Conditioned Re-exposed rats were compared to Not Conditioned Re-exposed and Conditioned Not Re-exposed rats. Freezing was observed in the Conditioned-Re-exposed group only. It was associated with an overall increase in Fos expression in the entire periaqueductal gray that was significantly greater than in the two other groups. The largest and most significant increase in Fos immunoreactivity was found in the ventrolateral column (especially in its caudal part), whereas only a moderate increase was found in the lateral column. The present results argue in favour of the ventrolateral column as the region of the periaqueductal gray that is preferentially involved in expression of conditioned fear. As previous lesion studies suggested, the ventrolateral periaqueductal gray may play a role in mediating the immobility component of freezing induced by fear. Other lines of evidence suggest that it may also play a role in mediating the quiescence immobility associated with deep pain. We propose that the ventrolateral column of the periaqueductal gray acts as an integrating centre mediating behavioural inhibition.

Animals↗

The epidemiology of diaphragmatic hernia.

We studied the epidemiology of diaphragmatic hernia based on 1439 cases collected from a French, a Swedish, and a California birth defect registry. This is the largest epidemiological material available up to now. Isolated diaphragmatic hernia existed in 875 infants, diaphragmatic hernia with associated malformations in 486, and with chromosome anomalies in 78. Among unilateral forms, right-sided hernias were found in about 20%, equally often in isolated and associated forms. There is a male excess of the same magnitude in isolated and associated forms but among the latter varying between programs. There was a change in the sex distribution of associated cases in California before 1988 and after which is not fully explained. The twinning rate is increased and is similar in isolated and associated forms. There is no marked effect of maternal age or parity on the risk of diaphragmatic hernia. Except for well-known conditions, no specific combination of associated malformations was found. Marked differences in recorded rates were found between the programs but not between races within the California program. The differences appear to a large extent to be due to different ascertainment, also apparent in different survival rates. Marked variations in rate with time is seen in the two programs with an extended observation time, again at least partly explainable by varying ascertainment.

California↗

Effect of eliminating seropositive canines on the transmission of visceral leishmaniasis in Brazil.

In Brazil, where Leishmania chagasi causes endemic American visceral leishmaniasis (AVL), the spread and maintenance of human disease are attributed to canine reservoirs. However, despite measures directed toward the elimination of infected canines, the incidence of human disease continues to increase. To evaluate the role of infected canines in the acquisition of AVL by humans, we undertook a controlled intervention study in three similar, but isolated, valleys of Pancas, Espírito Santo, Brazil. In the two experimental (intervention) valleys, infected dogs were eliminated whereas in the control valley, seropositive canines remained untouched. During the 12-month study period, human seropositivity rates, as measured by dot enzyme-linked immunosorbent assay, increased from 15% to 54% in the intervention valleys and from 14% to 54% in the control valley. The elimination of infected canines in the intervention valleys did not result in a statistically significant difference between the incidences of human serological conversion in the intervention and control valleys at either 6 (20% and 22%, respectively; P = .5961) or 12 months (26% and 27%, respectively; P = .9442). The role of humans as a significant reservoir for AVL is proposed as an explanation for the study results.

Animals↗

A pathway to the GP: the pharmaceutical 'consultation' as a first port of call in primary health care.

OBJECTIVE: This study explored advice-giving behaviour of staff in community pharmacies in order to generate fresh insights into the nature, sequence and process of pharmacy consultations for minor ailment advice. METHOD: An ethnographic-style research strategy was used, combining staff and patient interviews, with non-participant observation of medicines and health-related interactions between pharmacy users and staff. One full week was spent in each of ten pharmacies. RESULTS: The study highlighted that patients use pharmacies for treatment of minor ailments, sometimes before going to the GP, and sometimes in preference to the GP. By matching remedies to conditions, community pharmacy staff play a major role in keeping minor ailments out of general practice, but act as an agent of referral in cases which merit a GP consultation. CONCLUSION: It is in the interests of GPs to 'exploit' the advisory role of the pharmacist. A two-way referral system would allow doctors to build on the professional skills of the pharmacist as an over-the-counter expert, while ensuring that pharmacists have a channel through which to filter patients with potentially serious illnesses.

Adolescent↗

Future indications for macrolides.

The antimicrobial spectrum of azithromycin and clarithromycin suggests a number of further uses for these newer macrolides. Favorable clinical and bacteriologic responses have been reported with both antibiotics in children with community-acquired pneumonia. Response rates were high for overall patient populations and for subgroups with infection caused by Mycoplasma pneumoniae and Chlamydia pneumoniae. Treatment with azithromycin or clarithromycin has resulted in a reduction in mycobacteremia and an improvement in clinical symptoms in adult AIDS patients with disseminated Mycobacterium avium-intracellulare complex. Prophylactic treatment with azithromycin may prevent M. avium-intracellulare complex, especially when combined with rifabutin. Preliminary evidence suggests that both azithromycin and clarithromycin in multidrug combinations may effectively eradicate Helicobacter pylori and that azithromycin may be useful in treating bacterial gastritis caused by Campylobacter species. Trachoma and infections caused by Bordetella pertussis and Ureaplasma urealyticum are other possible future indications for the newer macrolides. Limited clinical evidence also suggests that azithromycin may be effective in the prevention and treatment of malaria.

Acquired Immunodeficiency Syndrome↗

Anatomy, pathophysiology, and prevention of senile enophthalmia and associated herniated lower eyelid fat pads.

We describe in detail the anatomy and function of the "Lockwood suspensory ligament" and the interrelated function of the orbital contents responsible for the intraorbital position of the eyeball and fat. With age, or because of genetic disposition, the eyeball descends, reducing the space between it and the floor of the orbit. This will inevitably cause forward projection of the extraconical orbital fat, creating herniated fat pads and resulting in enophthalmia. Based on the volume of the bony orbit and its contents, it is likely that relocating, rather then removing, herniated fat pads will greatly improve and prevent the enophthalmia of aging and give the globe a position and a projection of youth. Based on the results of surgery using the capsulopalpebral flap, it is likely that a descended Lockwood suspensory ligament, rather than a weakened orbital septum, is the cause of herniated fat pads and enophthalmia. We feel neither a weakened orbital septum nor an overabundance of orbital fat nor a shallow orbit is responsible for either of these conditions. We give a detailed description of how to raise the globe, preserve and relocate herniated fat pads, and manage and prevent enophthalmia and obtain a beautiful, youthful looking eye.

Adipose Tissue↗

The expression of the gap junctional protein Cx43 is restricted to proliferating and non differentiated normal and transformed keratinocytes.

The passage of specific growth modulating signals through gap junctions may regulate the proliferation and differentiation of human keratinocytes. To investigate this, we correlated the proliferation of normal human keratinocytes and a transformed squamous cell carcinoma cell line, SCC4, with the expression of the gap junctional proteins Cx43, 31 and 31.1, known to be expressed by keratinocytes. Proliferation was confined to preconfluent and confluent cultures of normal keratinocytes, falling to undetectable levels once postconfluency was achieved. Cx43, at both the message and protein levels, paralleled these changes, being elevated predominantly in preconfluent and confluent cultures, and downregulated in postconfluency. Similar results were found for Cx31 and 31.1 at the message level. In contrast, the proliferation of SCC4 cells cultured in media supplemented with 5.0% FCS was maintained at a substantial level from preconfluency through 2 weeks postconfluency. Cx43, 31, and 31.1 RNA and Cx43 protein expression mirrored the levels of proliferation within SCC4 cultures. Cx26 and 32 were not found in normal keratinocytes or SCC4 cells at any stage of differentiation. These data, illustrating a tight correlation between proliferation and Cx43, 31 and 31.1 expression, suggest that these connexins may represent proliferation-specific gap junctions within keratinocytes, and may therefore transmit signals that control keratinocyte division.

Calcium↗

"Goodbye Dolly?" The ethics of human cloning.

The ethical implications of human clones have been much alluded to, but have seldom been examined with any rigour. This paper examines the possible uses and abuses of human cloning and draws out the principal ethical dimensions, both of what might be done and its meaning. The paper examines some of the major public and official responses to cloning by authorities such as President Clinton, the World Health Organisation, the European parliament, UNESCO, and others and reveals their inadequacies as foundations for a coherent public policy on human cloning. The paper ends by defending a conception of reproductive rights of "procreative autonomy" which shows human cloning to be not inconsistent with human rights and dignity.

Animals↗