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Biomedical subjects

R J Collins

Publications and source records attributed to R J Collins.

At least 19 recordsLinked to original sources
PubMed2000

Inhibition of MAP kinase kinase (MEK) results in an anti-inflammatory response in vivo.

The MAP kinase pathway has been well-characterized as a cascade of sequential protein phosphorylation events leading to the upregulation of a variety of genes in response to growth factors and mitogens. We are interested in the role of these kinases in inflammation and have thus examined their activity in vivo using TPA-induced ear edema in the mouse as a model of inflammation. We show that the activities of both ERK-1 and ERK-2 are upregulated in this model in response to TPA. Increased levels of ERK phosphorylation are measurable as early as 15 min poststimulation and reach a level 8-fold over controls at 4 h. In contrast, minimal activation of JNK or p38 is observed. Topical treatment of ears with the MEK inhibitor, U0126, prevents ERK phosphorylation and ear swelling in a dose-dependent manner in this model. These results suggest that the MEK/ERK pathway is important during an inflammatory response in vivo.

Animals↗
PubMed1998

Conservative treatment of low grade squamous intraepithelial lesions (LSIL) of the cervix.

OBJECTIVE: To assess the accuracy of the cervical smear and colposcopy in diagnosing low grade squamous intraepithelial lesions (LSIL), and the natural history of LSIL. METHOD: The cytological, colposcopic and histological findings of 145 patients with a smear diagnosis of LSIL were compared, and the final outcome studied. RESULTS: The diagnosis of LSIL either by cytology alone or in combination with colposcopy was associated with a rate of overdiagnosis of 11.7% and 6.9%, respectively, and a rate of underdiagnosis of 31.0% and 26.2%, respectively. Spontaneous regression of lesions occurred in 81.1% of patients with proven LSIL, with regression within 24 months in 4/5 of cases. CONCLUSIONS: The degree of dysplasia shown in the cervical smear correlated poorly with histology. All patients with cervical smear showing LSIL should have colposcopy and colposcopic-directed biopsy to exclude the presence of more advanced lesions. In the absence of some serious lesions, it is then acceptable to observe the patient for 24 months before adopting definite treatment, as spontaneous regression is common.

Adult↗
PubMed1997

Diagnostic significance and possible pitfalls of nuclear grooves in extrathyroid cytology.

The diagnostic significance of grooved nuclei in the cytology of extrathyroid lesions is not well-described in the literature. Isolated cases of metastatic adult granulosa cell tumor, reactive mesothelial hyperplasia, Langerhans' cell histiocytosis, recurrent renal cell carcinoma, and round cell liposarcoma were reviewed, and their cytologic features were discussed. While nuclear grooving can be present to a different extent in all these conditions, the significance of this feature in diagnostic cytology varies. The integration of clinical information, radiologic findings, different morphologic features, and immunohistochemistry is necessary before a final conclusion is reached.

Adolescent↗
PubMed1997

Cutaneous epithelioid angiosarcoma: a potential diagnostic trap for cytopathologists.

We report on the cytologic features of a rare case of cutaneous epithelioid angiosarcoma of the scalp occurring in a 65-yr-old Chinese male. The prominent epithelioid features may cytologically mimic poorly-differentiated carcinoma, malignant melanoma, and even epithelioid sarcoma. Recognition of subtle cytologic features of vasoproliferation, immunohistochemical demonstration of endothelial markers, and ultrastructural examination are necessary before a final conclusion may be drawn.

Aged↗
PubMed1996

A melanoma cell line sensitive to expression of a fusion protein binding the retinoblastoma protein family pocket domain.

An established melanoma cell line (MM96L) was transfected with selectable plasmid constructs encoding either whole SV40 large T antigen, or beta-galactosidase fusions with the retinoblastoma protein (Rb)-binding region of SV40 large T antigen and a nonbinding mutant derivative of it. Both of the beta-galactosidase fusions also encoded the large T nuclear targeting signal. Transcription of inserted genes was regulated through a Zn+2-inducible metallothionein IA promoter, which provides tight but not absolute control of expression. Only the wild-type large T segment fusion was functionally active in the binding of Rb protein. Stable lines derived from primary transfectants with the expression plasmid encoding the mutant large T segment fusion showed a normal FACS scan profile, a normal growth rate, and (upon induction) high levels of nuclear staining for beta-galactosidase. However, cells transfected with the wild-type (Rb-binding) large T segment fusion grew slowly, with surviving clones assuming a predominantly tetraploid karyotype and relatively much lower levels of beta-galactosidase activity upon Zn+2 induction. The latter cells, but not those transfected with the corresponding non-Rb-binding fusion construct, also exhibited elevated cell death and apoptosis in response to the inducer Zn+2. These results implied that expression of an Rb-binding protein has deleterious effects on the melanoma cell line growth and may reflect a role for Rb of a related pocket protein in maintaining the differentiation state of these transformed cells.

Amino Acid Sequence↗
PubMed1996

Cytologic Diagnosis of "CASTLE" of thyroid gland: report of a case with histologic correlation.

We report on the cytologic and histologic features of a rare form of lymphoepithelioma-like carcinoma of the thyroid i.e., carcinoma showing thymus-like element (CASTLE). Sixteen cases of cervical lymph node aspirates with metastatic nasopharyngeal carcinoma are also reviewed. While it is important to recognize CASTLE of the thyroid because of its distinctly good prognosis, its cytologic features closely resemble those in metastatic nasopharyngeal carcinoma.

Adult↗
PubMed1995

Renal abnormalities and an altered inflammatory response in mice lacking cyclooxygenase II.

Prostaglandins have wide-ranging effects in the body and are thought to be important mediators of inflammation. Cyclooxygenase (COX) plays a key regulatory role in prostaglandin synthesis, and occurs in both constitutive (COX-1) and inducible (COX-2) isoforms. COX-1 is thought to provide cytoprotective effects, whereas COX-2 is both inducible and the major isoform of inflammatory cells. Reduction of prostaglandin production by inhibition of cyclooxygenases appears to be the main mechanism of action of most non-steroidal anti-inflammatory drugs (NSAIDS). Here we present an animal model of COX-2 deficiency that was generated by gene targeting. Defects in null mice correlating with reduced viability included renal alterations, characteristic of renal dysplasia (100% penetrance), and cardiac fibrosis (50% penetrance). Female Cox-2-/- mice were infertile. COX-2 deficiency failed to alter inflammatory responses in several standard models, but striking mitigation of endotoxin-induced hepatocellular cytotoxicity was observed.

Animals↗
PubMed1994

Fine-needle aspiration biopsy of pilomatrixoma: still a diagnostic trap for the unwary.

Of the 16 cases of fine-needle aspiration biopsy (FNAB) of pilomatrixomas reported since 1982, only 25% were correctly diagnosed prior to excision. The most common pitfall encountered was a false-positive or suspicious diagnosis of a carcinoma. All the reported cases had a polymorphous cellular and noncellular composition on low-power examination, including numerous basaloid cells, ghost cells, squamoid cells, foreign body giant cells, mixed inflammatory cells, keratin clumps, and granular debris which might be easily mistaken for a malignant necrotic background. Amongst these, ghost cells were the critical pathognomonic feature. This paper reported a further finding that had been underemphasized in the literature: masses of refractile orangeophilic keratin clumps representing compact sheets and stacks of ghost cells. Their presence should alert the observer to search for the more diagnostic dispersed forms which otherwise might be inconspicuous and easily overlooked.

Adult↗
PubMed1994

A flow cytometric study of cell death: failure of some models to correlate with morphological assessment.

The balance between cell death and cell proliferation is a significant factor in the growth kinetics of normal and neoplastic tissues. Distinction between the two major forms of cell death, necrosis and apoptosis, is now recognized as important in understanding mechanisms regulating cell survival. A recent approach in the study of apoptosis has been the use of flow cytometry, with some reports indicating that, when stained with propidium iodide (PI), the DNA of apoptotic cells has decreased fluorescence compared with that of viable cells. In this study, we investigated a flow cytometric procedure which used the simultaneous analysis of DNA content and 90 degrees light scatter (90LS). Significant differences in the PI staining pattern and a shift in 90LS were observed when apoptotic death occurred at different stages of the cell cycle. Importantly, such differences only allowed accurate quantification of apoptosis when it occurred in G1. While necrosis could be distinguished from apoptosis when examined during its early stages, a similar staining pattern to that found with apoptosis was observed when necrosis was examined during its latter stages. The results indicate that the measurement of DNA staining cannot be exclusively relied upon to detect apoptosis occurring in all models. However it is useful in the investigation of this process when the death occurs in G1, in that the method offers a rapid means for quantification.

Animals↗
PubMed1994

Assessment of cell proliferation in hydatidiform mole using monoclonal antibody MIB1 to Ki-67 antigen.

AIMS: To assess the role of Ki67 immunoreactivity in predicting the clinical progress of hydatidiform mole. METHODS: Tissue from 87 hydatidiform moles, 11 normal first trimester placentas, 11 normal term placentas and 17 spontaneous abortions were examined for expression of Ki67 antigen, using the monoclonal antibody MIB1. RESULTS: Ki67 immunoreactivity was significantly higher in the tissue from normal first trimester placentas than in that from normal term placentas and spontaneous abortions. Among the 87 patients with hydatidiform moles studied, 20 developed persistent gestational trophoblastic disease and required subsequent treatment. There was no statistically significant difference in the Ki67 index between the 20 patients who developed persistent disease and those who did not. CONCLUSION: Hydatidiform moles which give rise to persistent trophoblastic disease do not have a higher proliferative rate than those which do not. The Ki67 index is not useful for predicting the prognosis of molar pregnancies.

Abortion, Spontaneous↗
PubMed1994

Ultrasound guided transperineal prostatic aspiration biopsy: experience in Hong Kong.

OBJECTIVE: The purpose of this study is to correlate the result of the ultrasound guided transperineal aspiration biopsy with the clinical findings. MATERIALS AND METHODS: We retrospectively studied 27 patients who had been subjected to ultrasound guided transperineal prostatic aspiration biopsy in our institution during the period 1990 to 1992. The patients were divided into two groups: Group A--those with clinically palpable nodules on digital examination, and Group B--those without palpable nodule but with clinical evidence of prostatic enlargement and/or bladder outlet obstruction. RESULTS: There were 8 biopsy proven cancers, 4 of them were palpable lesions while the other 4 were clinically non-palpable. The overall positive predictive value was 29.6%; this increased to 40% if the lesions were palpable but decreased to 23.5% if the lesions were non-palpable. CONCLUSION: The overall positive predictive value of this technique was found to be consistent with other studies using different methods of biopsies. The positive predictive value was increased if the abnormality was clinically palpable. This technique was also found to be safe and no significant complication was observed in these patients.

Aged↗
PubMed1994

Expression of the p53 gene in trophoblastic cells in hydatidiform moles and normal human placentas.

In this study we compared the expression of p53 in six early placentas and eight hydatidiform moles using Northern blotting. A higher expression of p53 in hydatidiform moles as compared to normal placentas of comparable gestational age was observed. Immunohistochemical studies did not detect mutant protein of p53 in the hydatidiform moles. DNA sequencing was performed on four of the hydatidiform moles with increased expression of p53, but no mutations could be detected. The possible role of p53 in the pathogenesis of hydatidiform mole is discussed.

Base Sequence↗
PubMed1993

Antagonism of cocaine self-administration by the preferential dopamine autoreceptor antagonist, (+)-AJ 76.

(+)-AJ 76 is a presumed preferential dopamine (DA) autoreceptor antagonist which, in previous behavioral investigations, has displayed properties characteristic of both DA agonists and DA antagonists. In an attempt to test the hypothesis that (+)-AJ 76 might be an effective cocaine pharmacotherapy, the present experiments evaluated (+)-AJ 76's behavioral profile in 3 standard reinforcement paradigms. In the first experiment, (+)-AJ 76 paralleled a DA antagonist in that it failed to support self-administration behavior at all doses (0.1, 0.32, and 1.0 mg/kg/inj) tested. In the second experiment, (+)-AJ 76 (0.9, 3.5, and 14.0 mg/kg) closely resembled the DA agonist D-amphetamine (0.25, 1.0, and 4.0 mg/kg) in producing a clear dose-dependent conditioned place preference. In the third experiment, (+)-AJ 76 (1.88, 3.75, 7.5, 15.0, and 30.0 mg/kg) significantly reduced breaking points (BPs), increased rates of responding, and delayed the onset of responding for cocaine. While (+)-AJ 76 mimics a typical DA antagonist in its ability to reduce BPs and augment rates of responding for cocaine, recent evidence suggests that it more closely resembles a DA agonist in its ability to delay the onset of responding for cocaine. In summary, the present investigations have shown that (+)-AJ 76's profile in 3 reinforcement paradigms is unusual and not exclusively representative of either DA agonists or DA antagonists. The potential utility for such an agent in treating cocaine abuse is discussed.

Animals↗