A human oral tumour progression model was established that consists of normal epithelial cells and three cell lines representing stages from dysplastic to metastatic cells. To investigate the impact of exogenous transforming growth factor-beta 1 on this model system, we analysed the responsiveness of those cells to transforming growth factor-beta 1 and explored the potential mechanism underlying the transforming growth factor-beta 1 activity. We found that the growth of all cell types, regardless of their stage of tumour progression, is inhibited by transforming growth factor-beta 1, although to different degrees. Transforming growth factor-beta 1 induced the expression of cyclin-dependent kinase inhibitors p15(INK4B), p21WAF1/(CIP1) and p27(KIP1). In contrast, transforming growth factor-beta 1 was found to stimulate the invasive potential of one cell type that represents the most advanced stage of tumour phenotype, suggesting that the impact of transforming growth factor-beta 1 on functional features of tumour cells other than cellular proliferation may play a significant role in the process of oral tumour progression.

Active Transport, Cell Nucleus↗

PubMed2002

A preliminary study on the effect of ultrasound therapy on the healing of surgically severed achilles tendons in five dogs.

This study was conducted on the left Achilles tendon in five clinically normal dogs. The Achilles tendon was surgically exposed and severed 3-4 cm proximal to the point of its insertion. Tenorrhaphy was undertaken by the application of three sutures on the various tendon units of the Achilles tendon using single locking-loop sutures with polyamide no. 1-0. The superficial digital flexor tendon was sutured with catgut using two horizontal mattress sutures. No ultrasound therapy was used in the animals of group I (control). Ultrasound therapy was given to the animals of group II (treated) starting from the third day post-operatively at 0.5 W/cm2 for 10 min daily for 10 days. A cortical screw was used for immobilization of the tibiotarsal joint which was removed 4 weeks after tenorrhaphy. Post-operatively, healing of the Achilles tendon was monitored using clinical observations, ultrasonography, gross and histomorphological observations at various intervals up to 120 days in both groups. Clinically, the dogs showed significant lameness for the first 4-5 days, which disappeared earlier in the ultrasound-treated (group II) animals than the controls (group I). Extension and flexion of the hock joint were found to be near normal at 6 weeks after the repair of the Achilles tendon. Ultrasonography showed anechoic to hypo-echoic echo-texture on days 3 and 7 after repair. By day 40, the echo-texture started to improve to hypo-echoic in group II, but in group I anechoic areas were still observed. However, the tendon showed near normal mottled hypo- to hyper-echoic texture in both groups by day 120. Gross observations suggested that the Achilles tendon in group II showed comparatively fewer adhesions than in group I animals. Histologically, in group II (treated), on day 40, the union was comparatively better without any inflammatory reaction. Bundle formation had begun in the ultrasound-treated animals which was not observed in the control animals. By day 90, more compact parallel bundle formation had taken place with minimum cellularity. Bundle formation was in its advanced stage in the treated animals. By day 120, the tendon tissue was comparatively acellular and looking like a normal tendon. The use of the cortical screw provided good immobilization and ultrasound therapy at 0.5 W/cm2 enhanced the Achilles tendon healing in dogs.

Achilles Tendon↗

PubMed2002

Anti-inflammatory and antimicrobial activities of triterpenoids from Strobilanthes callosus nees.

The anti-inflammatory and antimicrobial activities of the 95% ethanol extract, benzene fraction and isolated triterpenoids of Strobilanthes callosus were investigated. In the carrageenan-induced paw edema inflammation model, the taraxerol showed a high reduction of edema, but the antimicrobial effect observed was lower at the two doses employed. These results confirm the use of this plant in folk medicine as an anti-inflammatory and antimicrobial herbal drug.

Acanthaceae↗

PubMed2002

Monitoring expression of HER-2 on circulating epithelial cells in patients with advanced breast cancer.

Nineteen breast cancer patients with measurable metastatic disease who were starting an initial or new line of therapy were evaluated for circulating epithelial cells (CECs) a minimum of 4 times over the course of treatment. In 7 of the 10 CEC+ patients, HER-2 expression was detected on the CECs. CECs expressing HER-2 varied among patients and in serial samples from the same patient including a shift from HER-2- to HER-2+ CECs. These results demonstrate that it is possible to quantify receptors essential for rationally designed therapy using CECs and that reliance on the immunophenotype of the primary tumor can be misleading.

Breast Neoplasms↗

PubMed2002

Universal immunization of infants with low doses of a low-cost, plasma-derived hepatitis B vaccine in South Africa.

OBJECTIVE: To evaluate the effectiveness of universal vaccination against viral hepatitis B in South Africa among 18-month-old rural children. METHODS: Children were immunized with a course of low-dose (1.5 microg), plasma-derived hepatitis B vaccine at 6, 10 and 14 weeks of age, and blood samples from the children were tested for three hepatitis B markers: hepatitis B surface antigen (HBsAg), anti-HBs and anti-HBc. FINDINGS: One year after vaccination, a protective anti-HBs antibody titre of at least 10 IU/l was present in 669/769 (87.0%) of blood serum samples tested. Only 3/756 children (0.4%) were HBsAg positive and a fourth child was anti-HBc positive (HBsAg negative). This is a marked decrease compared to the hepatitis B prevalences reported in previous studies. Among rural migrant mine-workers, for example, HBsAg prevalence was 9.9%, and was 10.1% among children 0-6 years of age in the Eastern Cape Province. CONCLUSION: The low-dose, plasma-derived hepatitis B vaccine, which is affordable to most developing countries, was very successful in controlling endemic hepatitis B infection, where the virus is predominantly spread by horizontal transmission among infants and young children.

Biomarkers↗

PubMed2002

Isolated pancreatic tuberculosis and obstructive jaundice.

Explore the source record for details and available documents.

Adult↗

PubMed2002

Limited thoracoscopic ganglionectomy for primary hyperhidrosis.

Sympathetic ganglionectomy is universally accepted as an effective and enduring treatment for primary hyperhidrosis. However, the variable extent of the ganglionectomy to treat this condition has been reported to be associated with a troublesome compensatory hyperhidrosis in between 22% and 81% of patients. In this prospective evaluation of a limited second thoracic ganglionectomy this approach, in addition to always being effective for pallmar hyperhidrosis, proved useful in up to 90% of patients with associated axillary and plantar hyperhidrosis. A compensatory hyperhidrosis rate of 13% was noted, confirming that a limited ganglionectomy should be standard practice in the management of primary hyperhidrosis.

Adolescent↗

PubMed2001

A critical review of the probable reasons for the poor variable bioavailability of rifampicin from anti-tubercular fixed-dose combination (FDC) products, and the likely solutions to the problem.

The problem of poor/variable bioavailability of rifampicin, which is shown in particular when the drugs are present in anti-tubercular fixed-dose combination (FDC) products, is a matter of serious concern. There is a potential of failure of therapy in patients with an active disease. It perhaps also is a contributory factor towards the increasing resistance to anti-tubercular drugs. Unfortunately, the origin and cause of the problem is not clearly understood, though GMP and crystalline changes in the drug are invariably cited as the principal reasons. In this write-up, various probable physical and/or chemical reasons are critically reviewed. The enhanced decomposition of rifampicin in the presence of isoniazid in stomach after ingestion is indicated to be the key factor behind the problem. Some simple solutions offered by the knowledge of the cause are discussed and it is concluded that there is a need to have a multifaceted approach to handle the problem.

Animals↗

PubMed2001

Selective bilateral hippocampal volume loss in chronic schizophrenia.

BACKGROUND: The hippocampus is implicated in the pathophysiology of schizophrenia; however, volumetric changes are subtle and have limited diagnostic specificity. It is possible that the shape of the hippocampus may be more characteristic of schizophrenia. METHODS: Forty-five patients with chronic schizophrenia and 139 healthy control subjects were scanned using magnetic resonance imaging. Hippocampi were traced manually, and two-dimensional shape information was analyzed. RESULTS: Two shape factors were found to be adequate to represent variance in the shape of the hippocampus. One of these factors, representing volume loss behind the head of the hippocampus, provided a degree of discrimination between patients with chronic schizophrenia and healthy control subjects; however, overall hippocampal volume following appropriate adjustment for brain volume showed a similar level of discrimination. Patients with chronic schizophrenia were best characterized using these two measures together, but diagnostic specificity was only moderate. CONCLUSIONS: This study identified that less of the hippocampus was distributed in its posterior two-thirds in patients with chronic schizophrenia, and specifically in the region just posterior to the hippocampal head. Group discrimination on the basis of hippocampal volume and shape measures was moderately good. A full three-dimensional analysis of hippocampal shape, based on large samples, would be a useful extension of the study.

Adolescent↗

PubMed2001

A longitudinal study of hippocampal volume in first episode psychosis and chronic schizophrenia.

Brain abnormalities have been identified in patients with schizophrenia, but what is unclear is whether these changes are progressive over the course of the disorder. In this longitudinal study, hippocampal and temporal lobe volumes were measured at two time points in 30 patients with first episode psychosis (mean follow-up interval=1.9 years, range 0.54-4.18 years) and 12 with chronic schizophrenia (mean follow-up interval=2.3 years, range 1.03-4.12 years) and compared to 26 comparison subjects (mean follow-up interval 2.2 years, range 0.86-4.18 years). Hippocampal, temporal lobe, whole-brain and intracranial volumes (ICV) were estimated from high-resolution magnetic resonance images. Only whole-brain volume showed significant loss over the follow-up interval in both patient groups. The rate of this volume loss was not different in the first episode group compared to the chronic group. There were no changes in either hippocampal or temporal lobe volumes. The negative findings for the hippocampus and temporal lobes may mean that the abnormalities in these regions are stable features of schizophrenia. Alternatively, the period before the onset of frank psychotic symptoms may be the point of greatest risk for progressive change.

Adolescent↗

PubMed2001

Letrozole is more effective neoadjuvant endocrine therapy than tamoxifen for ErbB-1- and/or ErbB-2-positive, estrogen receptor-positive primary breast cancer: evidence from a phase III randomized trial.

PURPOSE: Expression of ErbB-1 and ErbB-2 (epidermal growth factor receptor and HER2/neu) in breast cancer may cause tamoxifen resistance, but not all studies concur. Additionally, the relationship between ErbB-1 and ErbB-2 expression and response to selective aromatase inhibitors is unknown. A neoadjuvant study for primary breast cancer that randomized treatment between letrozole and tamoxifen provided a context within which these issues could be addressed prospectively. PATIENTS AND METHODS: Postmenopausal patients with estrogen- and/or progesterone receptor-positive (ER+ and/or PgR+) primary breast cancer ineligible for breast-conserving surgery were randomly assigned to 4 months of neoadjuvant letrozole 2.5 mg daily or tamoxifen 20 mg daily in a double-blinded study. Immunohistochemistry (IHC) for ER and PgR was conducted on pretreatment biopsies and assessed by the Allred score. ErbB-1 and ErbB-2 IHC were assessed by intensity and completeness of membranous staining according to published criteria. RESULTS: For study biopsy-confirmed ER+ and/or PgR+ cases that received letrozole, 60% responded and 48% underwent successful breast-conserving surgery. The response to tamoxifen was inferior (41%, P =.004), and fewer patients underwent breast conservation (36%, P =.036). Differences in response rates between letrozole and tamoxifen were most marked for tumors that were positive for ErbB-1 and/or ErbB-2 and ER (88% v 21%, P =.0004). CONCLUSION: ER+, ErbB-1+, and/or ErbB-2+ primary breast cancer responded well to letrozole, but responses to tamoxifen were infrequent. This suggests that ErbB-1 and ErbB-2 signaling through ER is ligand-dependent and that the growth-promoting effects of these receptor tyrosine kinases on ER+ breast cancer can be inhibited by potent estrogen deprivation therapy.

Antineoplastic Agents↗

PubMed2001

Parasitic procrastination: late-presenting ovale malaria and schistosomiasis.

A 29-year-old woman with ovale malaria (most likely contracted, together with asymptomatic schistosomiasis, in East Africa two years previously) had fever, nausea and confusion, jaundice, anaemia, thrombocytopenia, hyponatraemia and hypokalaemia. She was initially diagnosed with and treated for blood-smear-positive vivax malaria. Because of the unusual clinical presentation, blood was analysed by a malaria species-specific nested polymerase chain reaction (PCR) assay which identified Plasmodium ovale as the only infecting species. This case illustrates (i) that a detailed travel history remains a vital part of clinical assessment, (ii) ovale malaria can have an exceptionally long incubation period and features of a moderately severe acute infection, and (iii) PCR assay may prove a valuable adjunct to blood film examination in the diagnosis and speciation of malaria.

Adult↗

PubMed2001

CD134L expression on dendritic cells in the mesenteric lymph nodes drives colitis in T cell-restored SCID mice.

Transfer of CD45RB(high) CD4+ T cells to immune-deficient mice in the absence of regulatory T cells leads to a Th1-mediated colitis. In this study, we show that intestinal inflammation is characterized by a 15-fold increase in the number of CD134L+ (OX40L+)-activated DC in the mesenteric lymph nodes (MLNs) compared with BALB/c mice. This was important functionally, as administration of an anti-CD134L mAb inhibited the proliferation of T cells in the MLNs as well as their expression of the gut-homing integrin alpha(4)beta(7). Most importantly, the anti-CD134L mAb completely blocked development of colitis. Surprisingly, CD134L was found to be expressed by a proportion of dendritic cells (DC) in the MLNs of unreconstituted SCID mice, suggesting that CD134L can be induced on DC in the absence of T cell-derived signals. These results indicate that some DC in the MLNs of SCID mice express an activated phenotype and that CD134L expression by these cells is involved in the development of colitis induced by T cell transfer. Accumulation of CD134L+ DC was inhibited by cotransfer of regulatory T cells, suggesting that inhibition of the accumulation of activated DC is one mechanism by which these cells prevent immune pathology.

Animals↗

PubMed2001

Molecular cytogenetic characterization of head and neck squamous cell carcinoma and refinement of 3q amplification.

We applied a combination of molecular cytogenetic methods, including comparative genomic hybridization (CGH), spectral karyotyping (SKY), and fluorescence in situ hybridization, to characterize the genetic aberrations in a panel of 11 cell lines derived from head and neck squamous cell carcinoma and 1 cell line derived from premalignant oral epithelium. CGH identified recurrent chromosomal losses at 1p, 3p, 4, 8p, 10p, and 18q; gains at 3q, 5p, 8q, 9q, and 14q; and high-level amplification at 3q13, 3q25-q26, 5q22-q23, 7q21, 8q24, 11q13-q14, 12p13, 14q24, and 20q13.1. Several recurrent translocations including t(1;13)(q10;q10), t(13;13)(q10;q10), t(14;14)(q10;q10), i(8)(q10), and i(9)(q10) and breakpoint clusters at 1p11, 1q21, 3p11, 5q11, 5q13, 6q23, 8p11, 8q11, 9p13, 9q13, 10q11, 11q13, 13q10, 14q10, and 15q10 were identified by SKY. There was a good correlation between the number of aberrations identified by CGH and SKY (r = 0.69), and the analyses were both confirmatory and complementary in their assessment of genetic aberrations. Amplification at 3q26-q27 was identified in 42% of cases. Although SKY defined the derivation of 3q gain, the precise breakpoint remained unassigned. Positional cloning efforts directed at the amplified region at 3q26-q27 identified three highly overlapping nonchimeric yeast artificial chromosome clones containing the apex of amplification. The use of these yeast artificial chromosome clones as a probe for fluorescence in situ hybridization analysis allowed a detailed characterization and quantification of the 3q amplification and refinement of unassigned SKY breakpoints.

Carcinoma, Squamous Cell↗