Altered expression of transforming growth factor-β1 mrna and protein in mouse skin carcinogenesis

Transforming growth factor (TGF)-β1, whose gene is located on mouse chromosome 7, has been proposed to be involved in skin carcinogenesis. In the study presented here, we demonstrated that single topical treatments with different types of tumor promoters, i.e., the protein kinase C activator 12-O-tetradecanoylphorbol-13-acetate (TPA, 2 μg); the non–protein kinase C activators anthralin (22.6 μg), benzoyl peroxide (20 mg), and cumene hydroperoxide (1.2 mg); the first-stage tumor promoters 4-O-methyl-TPA (500 μg) and A23187 (166 μg); and the second-stage tumor promoter mezerein (2 μg) produced transient induction of TGF-β1 mRNA in SSIN (inbred SENCAR) mouse skin. The time of maximum induction varied from 3 to 12 h; the relative extent of induction was ranked as cumene hydroperoxide > benzoyl peroxide > anthralin > TPA > 4-O-methyl-TPA > mezerein > A23187. These findings suggested that TGF-β1 mRNA induction is a common response of skin to several types of complete and stage-specific promoters; however, the extent of induction did not correlate with the reported hyperplastic activity of single applications of these promoters. We also demonstrated that TGF-β1 mRNA expression in papillomas of SENCAR mice generally correlated with expression levels of cyclin D1, another gene on chromosome 7, and with stage of tumor progression. TGF-β1 mRNA expression was constitutively elevated in most squamous cell carcinomas from either initiation-promotion or complete carcinogenesis protocols. Cell lines established from carcinomas also overexpressed TGF-β1 mRNA. Immunohistochemical staining of tissue sections of normal and TPA-treated skin revealed the presence of extracellular TGF-β1 protein in the dermis and intracellular TGF-β1 protein in the epidermis, especially in the suprabasal layers. The staining patterns of papillomas varied, with 62 ± 13% of the tissue showing strong intracellular staining but only 25 ± 8% of the connective tissue staining for extracellular TGF-β1. Variable staining patterns were also found in carcinomas; some areas stained heavily for both the intracellular and extracellular forms of TGF-β1. Overall, 28 ± 6% of the tissue of the 12 analyzed carcinomas stained for the intracellular form and 18 ± 5% for the extracellular from of TGF-β1. © 1994 Wiley-Liss, Inc.     

Effect of 5-hydroxytryptamine on vagal C-fiber subtypes in guinea pig lungs

5-Hydroxytryptamine (5-HT, serotonin) evokes pulmonary reflexes partially by activating vagal bronchopulmonary C-fibers. In the guinea pig, vagal bronchopulmonary C-fibers arise from cell bodies situated in the nodose and the jugular ganglia. The nodose and the jugular C-fibers differ both pharmacologically and neurochemically, and may subserve different functions. In this study, we compared the effect of 5-HT on the nodose and jugular C-fibers with receptive fields within the guinea pig lungs. The nerve terminals of the vagal bronchopulmonary C-fibers were studied in an ex vivo isolated perfused lung nerve preparation using the extracellular recordings. All nodose C-fibers responded to transient administration of 5-HT (10 microM) and to the selective 5-HT3 receptor agonist, 2-methyl-5-HT (10 microM), with the action potential discharge. The selective 5-HT3 receptor antagonist ondansetron (10 microM) inhibited (by approximately 90%) the activation of the nodose C-fibers evoked by 5-HT (10 microM). In contrast to the nodose C-fibers, the jugular C-fibers were unresponsive or poorly responsive to 5-HT (n=9) and unresponsive to 2-methyl-5-HT (n=11). A direct action of 5-HT on the C-fiber neurons was supported using the whole cell patch clamp recordings from the isolated vagal sensory neurons retrogradely labeled from the lungs. Consistently with the studies on the nerve terminals, 5-HT (10 microM) induced inward current in nodose lung-specific capsaicin-sensitive neurons. Conversely, 5-HT was inefficient to stimulate the lung-specific jugular neurons. We conclude that in the guinea pig lungs, 5-HT selectively stimulates vagal nodose, but not jugular C-fibers via the 5-HT3 receptors in the neuronal membrane.     

Nocardiosis in Srinagarind Hospital, Thailand: review of 70 cases from 1996-2001.

OBJECTIVE: Nocardiosis is a common opportunistic infection found in both immunocompromised and immunocompetent patients. The clinical manifestations, underlying diseases, radiologic findings, antimicrobial susceptibility and treatment of nocardial infection are presented here. METHOD: A retrospective study at Srinagarind Hospital, Khon Kaen in Thailand was performed. Medical records from 1996-2001 were reviewed. RESULTS: There were 81 cases of nocardiosis during the study period but data of only 70 cases were available. 80% of cases were male. The mean age was 39.7+/-14.9 years. Underlying diseases were found in 80%, of which HIV infection was the most common (34.3%). The common clinical findings were fever, cough, and cutaneous abscess. The most common clinical syndrome was pleuropulmonary infection (44.3%), followed by skin and soft tissue infection (22.8%). Multiorgan dissemination was found in 11.4% of cases. The chest X-rays were abnormal in 46 cases (65.7%); alveolar and reticulonodular infiltration was common. Only 70% had positive cultures for Nocardia spp. The resistance rate of Nocardia isolates to trimethoprim-sulfamethoxazole (TMP-SMX) was very high (57.9%) in this study. Most of the patients (85.7%) were treated with antimicrobials, of which TMP-SMX was commonly used. In-hospital mortality was 20%. Most of the cases who died had dissemination, brain abscesses or infection with TMP-SMX-resistant strains. The long-term prognosis was good, with a treatment success rate of 93.75%. CONCLUSION: Nocardiosis is a common opportunistic infection in many immunocompromised conditions. It can present with various clinical syndromes, especially pleuropulmonary infection. Culture may not yield the organism but modified acid-fast staining is very helpful in diagnosis. Drug susceptibility testing should be performed due to increasing resistance to TMP-SMX.     

The immunogenicity of intradermal influenza vaccination in COPD patients

We evaluated the immunogenicity of a reduced-dose intradermal trivalent, inactivated, split-virion seasonal influenza vaccine compared to that of a conventional intramuscular vaccination in chronic obstructive pulmonary disease (COPD) patients. One hundred and fifty-six COPD patients randomly received either 0.2 ml (6 μg hemagglutinin (HA) per strain) split into two-site intradermal (ID) injections or a single 0.5 ml (15 μg HA per strain) intramuscular (IM) injection. Geometric mean titers, seroconversion factors, seroconversion rates and seroprotection rates at 4 weeks post-vaccination in the ID group were less than those in the IM group. Only the seroconversion factor to influenza B in the ID group was statistically less than in the IM group (18.8 in the ID group, n = 81 versus 37.3 in the IM group, n = 75, p = 0.045). Nevertheless, each strain of the ID vaccination met all the Committee for Proprietary Medicinal Products (CPMP) criteria. Seroprotection rates were above 60% throughout the year in influenza A (H3N2), for at least 6 months in influenza A (H1N1) and at least 4 weeks in influenza B in both ID and IM groups. The reduced-dose intradermal vaccination may be considered for use in COPD patients in a vaccine shortage situation.     

What sort of men take garlic preparations?

A large prospective epidemiological study of middle-aged men has been in progress in South Wales over the last two decades. Information on medication use has been collected and shows a large increase in the number of men taking garlic preparations over this time. The group of men who take garlic are similar to the non-users in many ways but significant differences include lower levels of smoking, higher levels of alcohol consumption, some better dietary habits and a higher proportion with a history of hypertension.     

Factors associated with specific language impairment and later language development during early life: a literature review

It has been reported that 50% of children with specific language impairment (SLI) have persistent SLI, which has been associated with various risk factors. To date, however, there has not been a comprehensive review of studies into different risk factors that could be used by clinicians to facilitate parental counseling and individual case-management. Several studies about the factors associated with SLI were reviewed based on study design. This article presents a review of factors associated with later language development and SLI, and reviews the risk for children who have SLI during early life. The summary provides data including specific biologic and environmental factors that are significantly associated with SLI, to ensure early intervention for children with SLI in the presence of identified risk factors.