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Biomedical subjects

T Jennings

Publications and source records attributed to T Jennings.

At least 19 recordsLinked to original sources
PubMed2005

Nanometal surface energy transfer in optical rulers, breaking the FRET barrier.

Optical-based distance measurements are essential for tracking biomolecular conformational changes, drug discovery, and cell biology. Traditional Forster resonance energy transfer (FRET) is efficient for separation distances up to 100 A. We report the first successful application of a dipole-surface type energy transfer from a molecular dipole to a nanometal surface that more than doubles the traditional Forster range (220 A) and follows a 1/R(4) distance dependence. We appended a 1.4 nm Au cluster to the 5' end of one DNA strand as the energy acceptor and a fluorescein (FAM) to the 5' end of the complementary strand as the energy donor. Analysis of the energy transfer on DNA lengths (15, 20, 30, 60bp), complemented by protein-induced DNA bending, provides the basis for fully mapping the extent of this dipole surface type mechanism over its entire usable range (50-250 A). Further, protein function is fully compatible with these nanometal-DNA constructs. Significantly extending the range of optical based methods in molecular rulers is an important leap forward for biophysics.

Base Sequence↗
PubMed2001

Substance-abusing adolescents at varying levels of HIV risk: psychosocial characteristics, drug use, and sexual behavior.

PURPOSE: To evaluate the relationship of various psychosocial factors on HIV sexual risk behavior in a sample of 169 "inner city" male and female adolescents mandated into in court-ordered substance abuse treatment. METHOD: The Millon Adolescent Clinical Inventory (MACI) and measures of sexual behavior, condom attitudes and skills, HIV knowledge, and substance abuse were administered. Data were evaluated according to five HIV risk groups: abstinent (n = 37); monogamous and practicing only protected sex (n = 19); monogamous and practicing unprotected sex (n = 45); multiple partners and practicing only protected sex (n = 11); and multiple partners and having only unprotected sex (n = 57). RESULTS: Significant main effects were found for impulsive propensity, submissiveness, marijuana and alcohol use, condom attitudes, and intentions to engage in safer sex. Protective behavior was directly associated with submissiveness and inversely associated with impulsive personality profiles, with increased marijuana use emerging as a significant predictive factor in the choice for sexual activity vs. abstinence. More alcohol use was predictive of choosing multiple partners vs. monogamy. IMPLICATIONS: Factoring risk variation into the design of HIV psychosocial research may enhance the tailoring of effective prevention strategies.

Adolescent↗
PubMed2000

Inhaled nitric oxide improves survival in the rat model of high-altitude pulmonary edema.

OBJECTIVES: High-altitude pulmonary edema (HAPE) afflicts certain individuals after a rapid gain in elevation. Those susceptible demonstrate an exaggerated hypoxic pulmonary vasoconstrictive response. This causes pulmonary hypertension, which may disrupt vascular integrity. This experiment was designed to test whether inhaled nitric oxide would affect development of HAPE in a rat model. METHODS: Subjects were exposed in a hypobaric chamber to a simulated altitude of 6200 m (barometric pressure = 380 mm Hg, fraction of inspired oxygen = 0.19) for 24 hours. Control animals (n = 48) spontaneously breathed a mixture of 90% room air and 10% nitrogen, whereas the nitric oxide group (n = 48) received a similar mixture containing 83 ppm nitric oxide. Postmortem examination of lungs was performed for light microscopy, total hemoglobin, and gravimetric estimates of water content. RESULTS: Mortality was 39.5% (n = 19) in control animals and 6.2% (n = 3) in the nitric oxide group (P < .001). Both groups significantly increased their lung weight-body weight ratio. Percentage of lung water was similar in both groups despite increases in lung weight, which is consistent with the protein-rich edema characteristic of HAPE. Light microscopic examination of survivors' lungs in both groups revealed scattered alveolar hemorrhage. No significant cellular inflammatory response was present. CONCLUSIONS: We conclude that inhaled nitric oxide improves survival in the rat model of HAPE.

Administration, Inhalation↗
PubMed1999

The impact of training in problem-based interviewing on the detection and management of psychological problems presenting in primary care.

BACKGROUND: The vast majority of mental health problems present to primary care teams. However, rates of under-diagnosis remain worryingly high. This study explores a GP-centred approach to these issues. AIM: To examine the impact of training in problem-based interviewing (BPI) on the detection and management of psychological problems in primary care. METHOD: The detection and management of psychological problems by 10 general practitioners (GPs) who had received PBI training 12 months earlier was compared with that of 10 control GPs matched for age, sex, clinical experience, and practice setting; and had originally applied for, but had not been able to attend, BPI training. Consecutive attendees at one randomly selected surgery undertaken by each GP were invited to participate in the study. Two hundred and eighty patients living in Newcastle upon Tyne met inclusion criteria and gave informed consent. The presence or absence of psychological problems was assessed using patient self-ratings on the 28-item version of the General Health Questionnaire (GHQ) and blind independent observer ratings of the brief Present State Examination (PSE). Patient satisfaction with interviews was rated using the Medical Interview Satisfaction Scale (MISS). After each consultation, the GPs (blind to subjective and observer ratings) recorded their assessment and management of the patients' problems on a Practice Activity Card (PAC). RESULTS: In comparison with control GPs, index GPs demonstrated significantly greater sensitivity in the detection of psychological problems in the GHQ-PAC ratings. The absolute decrease in misdiagnosis of GHQ cases was 9% and of PSE cases was 15%. Patients meeting GHQ criteria for caseness were more likely to be prescribed psychotropic medication by an index GP than compared with a control GP. Length of interview did not differ between the groups and mean scores on the MISS suggested that patients attending PBI-trained GPs, compared with control GPs, were as satisfied or slightly more satisfied with their consultation. CONCLUSION: In comparison with control GPs, PBI-trained GPs were better at recognizing and managing psychological disorders. The potential benefits of BPI training are discussed in light of other attempts to improve mental health skills in primary care.

Adult↗
PubMed1996

Restricted patterns of CD44 variant exon expression in human papillary thyroid carcinoma.

CD44 is a polymorphic family of cell surface proteoglycans and glycoproteins implicated in cell-cell and cell-matrix adhesion interactions, cell migration, and tumor metastasis. CD44 exists as a standard form and as multiple isoforms arising from alternative splicing of variant exons (termed v1-v10) encoding parts of the extracellular domain. We demonstrated previously that papillary thyroid carcinomas exhibit aberrant patterns of alternative CD44 mRNA splicing (G. Ermak et al., Cancer Res., 55: 4594-4598, 1995). In the present report, we use reverse transcription-PCR using a new high-performance polymerase formulation (Ex Taq; TaKaRa Shuzo Co., Ltd., Otsu, Japan) , followed by Southern hybridization, and demonstrate that alternative exon usage in papillary thyroid carcinomas is restricted primarily to exons v6, v7, v8, v9, and v10, with weak expression of v3. Expression of v8 is tightly linked to v9 and closely related to v10 expression. Also, v6 and v7 expression are closely related. Papillary thyroid cancers exhibit a marked increase in specific mRNA species containing combinations of exons v6 to v10. Several isoforms found in papillary cancers are not detectable in histologically normal tissue derived from the corresponding contralateral thyroid lobes. Examples include a 750-bp v6- and v7-containing PCR product and a 650-bp v8- and v9- containing PCR product. Finally, a novel 530-bp PCR product was discovered and shown to contain a subsegment from exon 4 joined to a subsegment of exon 13 (v8), followed by the complete sequence of exons 14 (v9) and 15 (v10). This novel isoform was present in both the papillary cancers and contralateral tissues. In conclusion, papillary thyroid cancers exhibit specific patterns of aberrant alternative CD44 splicing, distinguishing them from histologically normal thyroid tissue.

Alternative Splicing↗
PubMed1996

Renal cortical neoplasm in a child with dialysis-acquired cystic kidney disease.

Acquired cystic disease of the kidney is a common phenomenon in long-term adult dialysis patients with endstage renal disease. Malignant degeneration with cortical neoplasms is also well documented in this patient population. Although the prevalence of this disease process is common in adults, the literature is sparse concerning its occurrence in children. To our knowledge, we report the youngest case of renal cortical neoplasm associated with dialysis-acquired renal cystic disease in a 13-year-old boy.

Adolescent↗
PubMed1996

Novel CD44 messenger RNA isoforms in human thyroid and breast tissues feature unusual sequence rearrangements.

CD44 is a family of cell surface proteins implicated in adhesion interactions and tumor metastasis. Multiple CD44 mRNA isoforms arise from alternative splicing of variant exons (termed v1-v10). We recently discovered a novel CD44 mRNA isoform in human papillary thyroid cancers featuring a junction between subsegments of exons 4 and 13 (v8). The sequence ACAG was repeated at both the donor and acceptor sites in the genomic DNA (G. Ermak et al., Cancer Res., 56: 1037-1042, 1996). We used reverse transcription-PCR to characterize expression of this isoform in a panel of thyroid lesions. In addition, we assayed three cryopreserved human breast cancers and two samples of normal breast tissue (from female subjects who had undergone cosmetic mammoplasty) to determine whether a similar isoform is present in breast carcinomas. Levels of the novel isoform were up-regulated in 88% of the goiters, adenomas, and papillary cancers, but were undetectable in cases of thyroiditis and absent or low-level in four samples of normal thyroid tissue. The three breast cancers each yielded a 546-bp PCR product that was not detected in normal breast tissue. The PCR product from one of the breast cancers was cloned, and sequence analysis revealed a novel mRNA isoform featuring a junction between exon 3 and an internal site within exon 13 (v8). The sequence GCTTCAG was repeated at both the donor and acceptor sites in the genomic DNA. These results show that human thyroid and breast tissues contain novel CD44 mRNA isoforms featuring unusual rearrangements at repeated sequences. Further studies are warranted to determine whether the expression of this class of isoforms correlates with growth status.

Breast↗
PubMed1995

Deregulated alternative splicing of CD44 messenger RNA transcripts in neoplastic and nonneoplastic lesions of the human thyroid.

CD44 is a polymorphic family of immunologically related cell surface proteoglycans and glycoproteins implicated in cell-cell and cell-matrix adhesion interactions, lymphocyte activation and homing, cell migration, and tumor metastasis. CD44 exists as a standard form and as multiple isoforms, each generated by alternative splicing of up to 10 variant exons (termed v1-v10) encoding parts of the extracellular domain. Using semiquantitative reverse transcriptase-PCR and Southern hybridization, alternative CD44 mRNA splicing was examined in 10 papillary thyroid carcinomas, 8 nodular goiters, 9 adenomas, 2 cases of thyroiditis, and 3 histologically normal thyroid controls. The amount of input cDNA for the CD44 PCRs was standardized against an internal control gene (glyceraldehyde phosphate dehydrogenase). Four papillary carcinomas showed significant overexpression of CD44 transcripts migrating between 750 and 1000 bp. These cases demonstrated reduced levels of the 482-bp standard isoform transcript. In six papillary cancers, we found a prominent v6-containing isoform at 750 bp that was present in only trace amounts in normal thyroid tissue. It is of interest that similar findings were seen in the majority of the goiters and adenomas but not in the cases of thyroiditis. These results show that deregulation of alternative CD44 splicing is a common feature of disordered thyroid follicular cell growth, both in neoplastic and nonneoplastic lesions. The data imply an important role for CD44, including CD44v6, in the pathogenesis of various thyroid lesions.

Adenocarcinoma, Papillary↗
PubMed1995

Nuclear p53 immunoreactivity in papillary thyroid cancers is associated with two established indicators of poor prognosis.

The tumor suppressor protein, p53, protects somatic cells against the accumulation of genomic alterations. Cells harboring mutant or inactivated wild-type p53 protein are at risk for the development of genomic instability. Nuclear accumulation of p53 protein is associated with the stepwise dedifferentiation of papillary carcinoma. We asked whether nuclear p53 accumulation is associated with two known indicators of poor prognosis in papillary carcinoma. We studied 55 consecutive papillary cancers (28 from Russia, and 27 from upstate New York). Nuclear p53 immunoreactivity was assessed using a monoclonal antibody, DO-1, on Formalin-fixed paraffin-embedded specimens. The DNA index was determined by computerized image analysis of Feulgen-stained sections. Nearly all cases were well differentiated and none were associated with distant metastases or extrathyroidal invasion. All primary lesions were less than 4 cm in diameter, and almost all patients were female. Nuclear p53 immunoreactivity was associated with a high-risk group characterized by two known indicators of poor prognosis: age > 50, aneuploid DNA content, or both. In the high-risk group (N = 24) 33% of cases displayed nuclear p53 positivity, compared with only 6% in a low-risk group (N = 31) which lacked both features (P = 0.015, two-tailed Fisher exact test). Nuclear accumulation of immunoreactive p53 protein is associated with two established indicators of poor prognosis in papillary carcinoma of the thyroid. This result is consistent with the idea that aberrations in p53 function are associated with the stepwise loss of differentiation in this cancer.

Adolescent↗
PubMed1995

Nuclear accumulation of MDM2 protein in well-differentiated papillary thyroid carcinomas.

Papillary thyroid cancer is the most common endocrine malignancy. Of all solid cancers presenting in adults, papillary thyroid cancer generally carries the best long-term prognosis. However, very little is understood about the molecular pathogenesis of this neoplasm. We recently hypothesized that increased nuclear levels of MDM2 protein might occur in well-differentiated papillary thyroid carcinomas (Gerasimov et al., Exp. Mol. Pathol. 62, 52-62, 1995). MDM2 is known to complex with and inactive the p53 tumor suppressor protein. Since p53 inactivation by gene mutation has an established role in the pathogenesis of undifferentiated (anaplastic) thyroid carcinoma, we reasoned that abrogation of p53 function by nuclear MDM2 protein accumulation might participate in the pathogenesis of certain well-differentiated thyroid cancers such as papillary cancer. In the present report we present the first direct evidence of MDM2 protein accumulation in the nuclei of papillary thyroid carcinoma cells in a subset of tumors. Using the IF-2 monoclonal antibody, which reacts specifically with human MDM2 protein, we studied 24 well-differentiated papillary thyroid carcinomas and 26 benign lesions (nodular goiters, adenomas, thyroiditis). Nuclear staining was quantitated using the CAS computerized image analysis system. We found positive nuclear MDM2 immunoreactivity in 8 (33%) of the carcinomas. In contrast, MDM2 staining was negative in all benign lesions (P = 0.001, two-tailed Fisher exact test). Normal thyroid tissue was also negative. These data suggest that nuclear accumulation of MDM2 protein might be implicated in the pathogenesis of a subset of papillary carcinomas. Further studies to investigate this possibility are warranted.

Adult↗
PubMed1995

P-glycoprotein expression in the squamous cell carcinoma of the tongue base.

P-glycoprotein (PGP), which is a product of the multidrug resistance gene (MDR1), is an active transmembrane efflux pump responsible for detoxifying normal cells as well as rendering tumor cells resistant to chemotherapy. It has also been implicated to be expressed by more aggressive cancers. It has not been well described in squamous cell carcinoma of the head and neck. In this investigation, an attempt was made to characterize advanced squamous cell carcinoma of the base of tongue with respect to expression of PGP. Using immunohistochemical techniques two anti-PGP monoclonal antibodies (JSB1 and C494) were used to detect PGP in these lesions, and an attempt was made to correlate levels of PGP staining and various tumor parameters. Usefulness of PGP in predicting survival and time to recurrence was also examined for these advanced lesions. All 33 base of tongue lesions showed staining for PGP with these monoclonal antibodies. This was the first study examining utility of C494 in detecting PGP in squamous cell carcinoma at this site. Increased level of PGP expression was seen in better-differentiated tumors as well as in tumors with diploid DNA. A trend of higher PGP expression and decreased survival emerged. This may represent a true relationship, but inherent heterogeneity of PGP expression within cells cannot be excluded. Both antibodies examined appear to be useful in the investigations of PGP distribution in squamous cell carcinomas of the head and neck sites by immunohistochemical techniques. Prognostic value of the level of PGP expression remains to be seen.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1990

Space adaptation syndrome is caused by elevated intracranial pressure.

Space adaptation syndrome (SAS) incapacitates about 50% of the astronauts with symptoms of headache, malaise, vomiting, vertigo, etc. A hypothesis that SAS is caused by elevated intracranial pressure secondary to the cephalad fluid shift in zero G is proposed. A mechanism of how the cephalad fluid shift could cause elevated intracranial pressure is discussed. Factors known to alleviate and exacerbate SAS are interpreted in light of the elevated intracranial pressure mechanism.

Adaptation, Physiological↗
PubMed1990

High-dose short-term chlorambucil for intractable sympathetic ophthalmia and Behçet's disease.

We treated five patients with intractable sympathetic ophthalmia and six patients with severe Behçet's disease by high-dose, short-term chlorambucil therapy. We used a total dose ranging from 306 mg to 4.2 g and a duration of therapy no longer than 36 weeks and in most cases less than 24 weeks. After termination of therapy all 11 patients had a sustained remission of their eye disease. Unless subretinal neovascularisation was present, all had a final visual acuity of 20/50 or better. Malignancy has not developed in any of our cases, with a follow-up ranging from 6 months to 12 years (mean, 4.5 years). Although 30- and 40-year follow-ups and larger numbers of patients may be necessary fully to realise the risks of chlorambucil, we believe that our high-dose, short-term regimen (Behçet's disease: average duration, 23 weeks; average total dose 2.2 g; sympathetic ophthalmia: average duration, 11 weeks; total average dose, 0.9 g) may be safer than previously reported chlorambucil regimens of one to two years or longer. In addition we fulfilled our aim of discontinuing all concomitant systemic corticosteroids within a relatively short time (usually six to eight weeks).

Adolescent↗
PubMed1990

Transscleral contact retinal photocoagulation with an 810-nm semiconductor diode laser.

Since the 810-nm wavelength has marked transmissibility through the sclera and absorption by melanin, it would be ideal for transscleral photocoagulation. We performed experiments to determine if consistent transscleral chorioretinal lesions could be produced in Dutch belted pigmented rabbits using the 810-nm laser, and if this modality caused less blood-retinal barrier disruption than retinal cryopexy of clinically equivalent treatment areas. The laser applications produced whitish to grayish-white retinal lesions when the surgeon, under direct visualization, used low powers and long durations (5 to 10 seconds), and controlled the treatment duration. Histopathologic evaluation of a lesion demonstrated an intact sclera overlying the chorioretinal lesion. Vitreous protein concentration, which was measured to assess blood-retinal barrier disruption, was significantly less in eyes treated with transscleral photocoagulation than in eyes treated with cryopexy of clinically equivalent treatment areas. We conclude that transscleral 810-nm laser treatment may be a viable clinical alternative to retinal cryopexy.

Animals↗
PubMed1989

Twenty cases of sympathetic ophthalmia.

We reviewed the charts of 20 patients with sympathetic ophthalmia who were seen in the uveitis clinic at the Eye and Ear Infirmary within an 11-year period. Of these 20 patients 14 maintained 20/50 or better visual acuity in at least one eye. We found early enucleation to be associated with a better visual prognosis, possibly due to earlier diagnosis and faster, more aggressive therapy rather than a reduction in antigenic load. The clinical appearance of Dalen-Fuchs nodules appears to indicate a more severe stage of disease. Chlorambucil was useful in patients with severe disease. To be effective and to lessen its side effects chlorambucil was given in daily dosages that were increased weekly over a short period to achieve bone marrow suppression. After a course of chlorambucil therapy intraocular inflammation could be controlled with topical steroids alone.

Adolescent↗
PubMed1989

Sympathetic ophthalmia following neodymium:YAG cyclotherapy.

Neodymium:YAG cyclotherapy has been demonstrated to lower intraocular pressure dramatically in patients with uncontrolled glaucoma, with potentially fewer side-effects than cyclocryotherapy. We report the clinical course and histopathological features of a case of sympathetic ophthalmia occurring soon after YAG cyclotherapy.

Adult↗