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Biomedical subjects

J Fine

Publications and source records attributed to J Fine.

At least 19 recordsLinked to original sources
PubMed2006

The value of T2 relaxation times to characterize lumbar intervertebral disks: preliminary results.

BACKGROUND AND PURPOSE: The present standard for staging intervertebral disk degeneration is a discrete scale, consisting usually of 5 stages. The purpose of this pilot study was to investigate the use of T2 measurements as a continuous measure of intervertebral disk degeneration. METHODS: We obtained images in 5 volunteers with a 3D fast spin-echo sequence modified for the purpose of calculating T2 relaxation times from multiple echoes in the echo train. Disks were classified on the basis of conventional criteria into one of the 5 stages of disk degeneration. Average T2 values were calculated for stage II, III, and V disks, which were identified in the volunteers. Differences between the disk levels were analyzed with analysis of variance and differences between stages tested with a Student t test with significance set at the 0.01 level. RESULTS: In the 5 volunteers, 20 stage II, 4 stage III, and a single stage V disk were found. Contour plots showed the highest T2 values in the nucleus pulposus near the vertebral endplates and lower T2 values in the intranuclear cleft region and peripheral annulus fibrosus. Average T2 values were significantly lower in the type III and V disks than in the normal disks. CONCLUSIONS: The study suggests that intervertebral disks can be characterized and classified accurately by means of T2 values. More studies are warranted to determine the range of T2 values for normal disks.

Adult↗
PubMed2003

Inhibition of experimental acute pulmonary inflammation by pirfenidone.

Pirfenidone, a putative tumor necrosis factor-alpha (TNF-alpha) inhibitor, has recently gained recognition for its therapeutic use in the treatment of idiopathic pulmonary fibrosis. As pulmonary fibrosis may be the result of lung inflammatory processes, we examined the anti-inflammatory potential of pirfenidone in several models of acute pulmonary inflammation. In antigen-induced allergic paradigms, 24 h after antigen challenge, sensitized mice or guinea pigs develop a prominent pulmonary inflammation, reflected by a significant increase in the number of recoverable bronchoalveolar lavage (BAL) total cells and eosinophils. In both species, the pretreatment of animals with pirfenidone (10 and 30 mg/kg) resulted in a dose-dependent inhibition of the antigen-induced pulmonary inflammation, which was reflected by a significant decrease in the BAL eosinophils and total cells by the 30 mg/kg dose. In a non-allergic model of pulmonary inflammation, rats challenged with intratracheal LPS develop a significant increase in BAL neutrophils and total cells, along with significant increases in TNF-alpha and IL-6. Pretreatment with pirfenidone (3 and 30 mg/kg) showed a dose-dependent inhibition of the LPS-induced pulmonary inflammation, reflected by a significant decrease in the number of BAL total and neutrophilic cells at both the 3 and 30 mg/kg dose. However, pirfenidone had no effect on the peak BAL levels of TNF-alpha. In contrast, pirfenidone significantly inhibited BAL levels of IL-6. In summary, we have shown that pirfenidone can inhibit allergic and non-allergic inflammatory cell recruitment and that its pulmonary anti-inflammatory activity is independent of TNF-alpha inhibition.

Animals↗
PubMed2001

Comparison of PDE 4 inhibitors, rolipram and SB 207499 (ariflo), in a rat model of pulmonary neutrophilia.

Using a rat model of lipopolysaccharide (LPS)-induced pulmonary inflammation, the antiinflammatory activity of SB 207499 was evaluated and compared to that of the prototypic type-4 phosphodiesterase (PDE4) inhibitor, rolipram. In dose-response experiments, we found that rats exposed to 10 microg or 100 microg of intratracheal (it) LPS developed a prominent pulmonary inflammation, due to a significant increase in the number of recoverable bronchoalveolar lavage neutrophils. The pulmonary neutrophilia, provoked by the challenge of 10 microg LPS/rat, was significant at 2 h, peaked by 16 h, declined thereafter but remained elevated for up to 48 h. Additionally, the exposure of rats to 10 microg LPS caused the local pulmonary production of TNF- alpha. In contrast to the cellular influx, TNF- alpha production peaked at 2 h and rapidly declined to negligible levels by 8 h. While low levels were detected, the levels of IL-1 beta in bronchoalveolar lavage did not significantly differ from saline challenged animals. Rats pretreated with rolipram or SB 207499, displayed dose-dependent inhibition of the LPS-induced pulmonary inflammation. Nevertheless, the pulmonary production of TNF- alpha and IL-1 beta was unaffected by either SB 207499 or rolipram. When provoked with the 10 microg dose of LPS, adrenalectomized rats produced a similar 24 h induction of pulmonary neutrophilia. Pretreatment of adrenalectomized rats with the PDE4 inhibitors showed similar inhibitory results to those obtained in normal rats. In summary, we have shown, using a rat model of LPS-induced pulmonary neutrophilic inflammation, that the inhibitory activities of rolipram or SB207499 are not linked to the production of TNF- alpha or the inhibition of IL-1 beta, and occur independently of endogenous catecholamine or corticosteroid release.

Adrenalectomy↗
PubMed2001

Ego atrophy in substance abuse: addiction from a socio-cultural perspective.

The use of intoxicants is indexed in American history adopting a social perspective of the role of alcoholism in traditional American society. Appealing to societal patterns, the elaboration of substance abuse as a disease is explored with a diagnostic focus on intervention as it relates to pathogenesis. Using clinical vignettes, the ego is proposed as the focus of pathology in the addiction process, featuring a regression to the defenses of projection and denial. Following the model proposed in Zinberg's seminal paper on addiction and ego function, various deficits are annotated that typify such regression. The ultimate clinical picture is one of ego atrophy, where basic interests and object relations are usurped by the all-consuming preoccupation with the substance of abuse.

Behavior, Addictive↗
PubMed2001

Methylphenidate selectively improves story retelling in children with attention deficit hyperactivity disorder.

OBJECTIVES: The goal of this study was to determine stimulant effects on story grammar, comprehension, and errors in the narratives of children with attention deficit hyperactivity disorder (ADHD) with and without comorbid language impairment. Previous research has demonstrated impairments in the narrative abilities of children with ADHD, but the effect of the primary treatment modality (methylphenidate) is unknown. METHODS: Fifty children with ADHD (7 to 12 years of age) were stratified for language impairment that might influence performance. In an acute, randomized, placebo-controlled crossover trial with two single doses (10 and 20 mg) of methylphenidate, the children listened to an audiotaped story while viewing a wordless picture book of the study, then retold the story and answered comprehension questions. The narratives were transcribed and coded for story grammar, length, and errors. RESULTS: Methylphenidate only increased children's reporting of the story characters' internal responses and attempts. It had no effect on story length or responses to comprehension questions. Responses to the factual questions were significantly more accurate than the inferential questions, irrespective of medication dose. Comorbid language impairment had no effect on performance or stimulant response. CONCLUSION: Story grammar analysis was sensitive to drug effects, which were subtle but specific and clinically meaningful. Results provide evidence for the theoretical linkage between internal responses and attempts.

Attention Deficit Disorder with Hyperactivity↗
PubMed2001

Human interferon-inducible 10-kDa protein and human interferon-inducible T cell alpha chemoattractant are allotopic ligands for human CXCR3: differential binding to receptor states.

The human CXC chemokines IP-10 (10-kDa interferon-inducible protein), MIG (monokine induced by human interferon-gamma), and I-TAC (interferon-inducible T cell alpha chemoattractant) attract lymphocytes through activation of CXCR3. In the studies presented here, we examined interaction of these chemokines with human CXCR3 expressed in recombinant cells and human peripheral blood lymphocytes (PBL). IP-10, MIG, and I-TAC were agonists in stimulating [(35)S]GTP gamma S binding in recombinant cell and PBL membranes but had no effect in the absence of hCXCR3 expression. (125)I-IP-10 and (125)I-I-TAC bound hCXCR3 with high affinity, although the (125)I-I-TAC B(max) value in saturation bindings was 7- to 13-fold higher than that measured with (125)I-IP-10. Coincubation with unlabeled chemokines decreased (125)I-IP-10 binding with a single discernible affinity. However, with (125)I-I-TAC, competition with IP-10 or MIG was incomplete, and multiple binding affinities were evident. Moreover, in contrast to I-TAC, IP-10 and MIG binding IC(50) values did not increase predictably with increased (125)I-I-TAC concentration in competition bindings, suggesting that these chemokines are noncompetitive (i.e., allotopic) ligands. Uncoupling of hCXCR3 eliminated (125)I-IP-10 binding but only decreased (125)I-I-TAC binding 30 to 80%, indicating that unlike IP-10, I-TAC binds with high affinity to uncoupled (R) and coupled (R*) hCXCR3. To examine chemokine binding to R*, we tested the effect of anti-hCXCR3 antibody on I-TAC- and IP-10-stimulated [(35)S]GTP gamma S binding. The antibody attenuated [(35)S]GTP gamma S binding in response to IP-10 but not to I-TAC, suggesting that the two chemokines bind differently to R*. Moreover, increased occupancy of R* with a >75-fold increase in (125)I -IP-10 concentration did not increase the I-TAC binding IC(50) value, and I-TAC increased the dissociation rate of (125)I-IP-10. From these data, we conclude that the binding of IP-10 and I-TAC to the R* state of hCXCR3 is allotopic.

Animals↗
PubMed2001

Enhanced expression of mucin genes in a guinea pig model of allergic asthma.

The ovalbumin (OVA)-sensitized guinea pig is often used as an animal model of asthma and airway hyperreactivity. A characteristic lesion of asthma is excessive production of mucin in the airways. Mechanistic studies of this lesion in guinea pigs have been limited due to lack of mucin gene probes for this species. The aim of the present study was to clone the cDNAs encoding two major airway mucins (Muc2 and Muc5ac) from the guinea pig, and investigate mucin gene expression in lungs of sensitized animals in response to antigen challenge. We isolated and sequenced two cDNA fragments coding for the sequences located within the carboxyl-terminal cysteine-rich region of guinea pig Muc2 and Muc5ac mucins. Comparison of cloned cDNAs with those from other species revealed high degrees of sequence identity and conservation of all cysteine residues in deduced primary sequences. Based on the resultant sequence information, we also designed oligonucleotide primers for specific detection of guinea-pig Muc2 and Muc5ac steady-state mRNA levels via reverse transcriptase/ polymerase chain reaction (RT-PCR). Levels of both Muc2 and Muc5ac mRNA in lungs of OVA-sensitized guinea pigs increased significantly by 30 min after an acute exposure to 0.3% OVA. In addition, levels of eotaxin mRNA also increased in these tissues, but the increases were not significant until 2 h after challenge. Correspondingly, the number of eosinophils in bronchoalveolar lavage fluid did not increase until 4 h postchallenge. Results of these studies suggest that the OVA-sensitized guinea pig responds to allergic challenge with enhanced expression of genes (e.g., eotaxin, Muc2, and Muc5ac) that likely play a role in increased airway inflammation and mucin overproduction, and enhanced mucin gene expression appears to occur before eosinophil infiltration.

Amino Acid Sequence↗
PubMed2001

Using language in psychiatry.

Much of the diagnosis and definition of psychiatric disorders depends on language behaviour. Both the lay and clinical communities recognize that some atypical language behaviour helps to the identify psychiatric disorders. A functional approach to language provides the means to classify the atypicalities in meaning and in wordings that are associated with psychiatric disorders. Culture levels, register, genre, context, vocabulary-grammar, and sound must all be taken into account in considering language atypicalities. Language simultaneously conveys 3 kinds of meaning--ideational, interpersonal and textual. Individually or combined, these 3 kinds of meaning can be used to describe the atypical language behaviour associated with psychiatric disorders.

Adult↗
PubMed2000

Long-term follow-up of unilateral pallidotomy in advanced Parkinson's disease.

BACKGROUND: Although the short-term benefits of posteroventral pallidotomy for patients with advanced Parkinson's disease have been well documented, little is known about the long-term outcome of the procedure. METHODS: We conducted a long-term follow-up study of a cohort of 40 patients who had undergone unilateral posteroventral medial pallidotomy between 1993 and 1996. Twenty patients were not evaluated because they had undergone a second surgical procedure (11 patients) or had died (2) or because they had dementia or another debilitating illness (4), lived too far away (1), or had been lost to follow-up (2). We conducted serial postoperative assessments of parkinsonism in the remaining 20 patients while they were taking medications ("on" period) and after overnight withdrawal of the drugs ("off" period). The mean follow-up time was 52 months (range, 41 to 64). RESULTS: The combined off-period score for activities of daily living and motor function on the Unified Parkinson's Disease Rating Scale was 18.0 percent better at the last evaluation than at base line (95 percent confidence interval, 4.9 to 31.0 percent; P=0.01). Significant improvements were also evident in the off-period scores for contralateral tremor (65.4 percent improvement, P=0.007), rigidity (43.2 percent, P=0.03), and bradykinesia (18.2 percent, P=0.04) and in the on-period score for contralateral dyskinesia (70.6 percent, P<0.001). Changes in medication did not contribute to the sustained improvement. The 20 patients who could not be included in the long-term analysis had similar base-line characteristics but a worse response to surgery at six months. CONCLUSIONS: In the group of patients with advanced Parkinson's disease who could be enrolled in our long-term follow-up study of unilateral posteroventral medial pallidotomy (20 patients from the original cohort of 40), significant early improvements in off-period contralateral signs of parkinsonism were sustained for up to five and a half years. There was a sustained significant improvement in on-period contralateral dyskinesia but not in other on-period signs of parkinsonism.

Activities of Daily Living↗
PubMed1999

Interleukin-10 enhances immune responses to pneumococcal polysaccharides and sheep erythrocytes in young and aged mice.

Antibody responses to pneumococcal polysaccharides are decreased in aged mice. Using a system to measure murine antibody responses to the Pnu-Imune vaccine, here we demonstrate that interleukin-10 (IL-10) has an adjuvant effect in enhancing the vaccine response in the aged. IL-10 increased the vaccine responses of B cells from aged mice in vitro only if either T cells or macrophages were also present. The need for T cells or macrophages could be substituted by cytokines such as IL-1 or IL-5, which are normally made by these accessory cells. Thus, IL-10 appeared to act on B cells directly but it worked in conjunction with other cytokines to induce an antigen specific response. In vivo studies showed that IL-10 administration enhanced antibody responses not only to thymic independent antigens but also to thymic-dependent antigens such as sheep erythrocytes. These data suggest that IL-10 may be useful in enhancing vaccine-specific responses in situations in which the host is immunocompromised.

Aging↗
PubMed1999

Cutting edge: species specificity of the CC chemokine 6Ckine signaling through the CXC chemokine receptor CXCR3: human 6Ckine is not a ligand for the human or mouse CXCR3 receptors.

The CC chemokine known as 6Ckine (SLC, Exodus-2, or TCA4) has been identified as a ligand for CCR7. Mouse 6Ckine has also been shown to signal through mouse CXCR3 and share some of the activities of IFN-gamma inducible protein 10 and monokine induced by IFN-gamma. Nonetheless, human 6Ckine has not been shown to bind CXCR3 receptor or have angiostatic activity. In this study, we report that human 6Ckine does not induce a calcium flux in either human CXCR3 or mouse CXCR3 transfected cells, although it is an equally potent agonist as mouse 6Ckine and human macrophage inflammatory protein-3beta in human CCR7 transfected cells. Mouse 6Ckine (but not human 6Ckine) is capable of competing with radiolabeled IFN-gamma inducible protein 10 for human CXCR3. In addition, radiolabeled human 6Ckine does not bind to either human CXCR3 or mouse CXCR3. Together these data suggest that human CC chemokine 6Ckine is not a ligand for the human or mouse CXC chemokine receptor CXCR3.

Animals↗
PubMed1999

Orthodontic and periodontal considerations in treatment of adult patients.

The coordination of orthodontics with periodontics in treating adult patients with high esthetic expectations is essential. In this article, three broad categories of relationships between the two specialties are described. In addition, several simple clinical situations illustrate how the interactions can help to improve the outcome of dental treatments.

Adult↗
PubMed1998

Validation of a melanoma prognostic model.

BACKGROUND: A "clinically accessible," 4-variable (patient age, patient sex, tumor location, and tumour thickness) prognostic model has been published previously. This model evaluated variables that were commonly available to the clinician. Because models are heuristic, validity of a prognostic model should be evaluated in a population different from the original population. OBJECTIVE: To evaluate the external validity of this 4-variable melanoma prognostic model. DESIGN: To estimate the external validity of this model, we used a population-based cohort of individuals with melanoma. We also evaluated a 1-variable model (tumor thickness). Estimates of the external validity of these logistic regression models were made using the c statistic and the Brier score. SETTINGS AND PATIENTS: A total of 1261 patients with melanoma evaluated in a multispecialty, university-based practice and 650 patients with melanoma from throughout Connecticut. MAIN OUTCOME MEASURE: Death from melanoma within 5 years of diagnosis. RESULTS: The c statistics for the 4-variable model were 0.86 (95% confidence interval [CI], 0.83-0.89) for the university-based practice data set and 0.81 (95% CI, 0.75-0.86) for the Connecticut data set. For thickness alone, the c statistics were 0.83 (95% CI, 0.80-0.86) and 0.79 (95% CI, 0.74-0.85), respectively. Brier scores for the 4-variable model were 0.09 (95% CI, 0.08-0.10) and 0.08 (95% CI, 0.06-0.09) and for the 1-variable model were 0.09 (95% CI, 0.08-0.10) and 0.08 (95% CI, 0.07-0.10), respectively. No significant differences exist between the data sets for the 4- and 1-variable models. CONCLUSIONS: The 4- and 1-variable models are generalizable. The simpler 1-variable model--tumor thickness--can be used with a relatively small loss in accuracy.

Female↗
PubMed1998

Sunlamp use and the risk of cutaneous malignant melanoma: a population-based case-control study in Connecticut, USA.

BACKGROUND: The relationship between cutaneous malignant melanoma and sunlamp use is examined in a Caucasian population in Connecticut, United States. METHODS: Cases were diagnosed between 15 January 1987 and 15 May 1987 with a first primary cutaneous melanoma. Controls were obtained from the general population, frequency matched to cases by sex and age, through random digit dialling of Connecticut telephone numbers. RESULTS: Of all study subjects, 141 (23%) cases and 95 (19%) controls reported ever having used sunlamps. The crude odds ratio (OR) for developing malignant melanoma after ever having used sunlamps was 1.30 (95% confidence interval [CI]: 0.97-1.74). This was reduced to 1.13 (95% CI: 0.82-1.54) after further adjusting for cutaneous phenotype and recreational sun exposure. Those who used more than one type of sunlamp had a threefold higher risk for melanoma compared to never users. Subgroup analyses showed that sunlamp use was associated with a greater increase in risk for melanoma among those who used sunlamps at home and those who were first exposed to sunlamps prior to 1971. The first use of sunlamps before the age of 25 showed somewhat higher risk for melanoma compared to first use later in life. CONCLUSION: The current study provides limited evidence that use of sunlamps increases the risk of melanoma. For future studies, it is crucial that type of sunlamp, year of first use and amount of exposure are all taken into account. The association between melanoma and tanning with both UV-A and UV-B lamps and tanning under sunlamps early in life merits further investigation.

Case-Control Studies↗
PubMed1997

Pituitary-directed leukemia inhibitory factor transgene forms Rathke's cleft cysts and impairs adult pituitary function. A model for human pituitary Rathke's cysts.

Leukemia inhibitory factor (LIF) and LIF receptors are expressed in adenohypophyseal cells and LIF regulates pituitary hormone transcription and cell replication in vitro. Therefore, transgenic mice expressing pituitary-directed LIF driven by the rat growth hormone (GH) promoter were generated to evaluate the impact of LIF on pituitary development. Three founders were established with diminished linear growth and body weight (57-65% of wild type [WT]), and intense anterior pituitary LIF immunoreactivity. Cystic cavities observed in pituitary anterior lobes were lined by cuboidal, ciliated epithelial cells, focally immunopositive for cytokeratin and S-100 protein and immunonegative for adenohypophyseal hormones. Transgenic pituitaries showed decreased GH (40%) and prolactin (PRL) (26%) cells, and decreased GH and PRL mRNAs by in situ hybridization. ACTH cells increased 2.2-fold, whereas gonadotrophs and thyrotrophs were unchanged. Serum GH was undetectable (< 0.78 ng/ml), PRL levels were one third of WT (P < 0.05), IGF-I levels were 30% of WT (P < 0. 001), and T4 was normal. 10 human pituitary Rathke's cysts studied all showed conclusive LIF immunoreactivity in cyst-lining cells. Thus, intrapituitary murine LIF overexpression causes cystic invaginations from the anterior wall of Rathke's cleft, suggesting failed differentiation of Rathke's epithelium to hormone-secreting cells. Arrested murine pituitary maturation with formation of pituitary Rathke's cleft cysts, GH deficiency, and short stature provide a model to study human Rathke's cyst pathogenesis.

Adrenocorticotropic Hormone↗