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Biomedical subjects

T Than

Publications and source records attributed to T Than.

16 recordsLinked to original sources
PubMed2001

Aromatic quinolinecarboxamides as selective, orally active antibody production inhibitors for prevention of acute xenograft rejection.

The prevention of xenograft rejection is substantially dependent on inhibiting antibodies (Ab) produced by B-cells independently of T-cell signals (TI-1). Due to their ubiquitous biochemical mechanisms of action, the immunosuppressants currently employed not only fail to discriminate between B- and T-cells but also have a narrow therapeutic window and, thus, their prolonged use in complex immunosuppressive regimens is problematic. By capitalizing on the target enzyme-bound (DHODH) structure 1b of one of these compounds, leflunomide, and modulating part of its multiple mechanisms of action to gain selectivity, the quinoline-8-carboxamide 3 was designed as a potentially weak enzyme inhibitor but effective immunosuppressant. Compound 3 fulfilled the mechanistic criteria set and had 10-fold B-cell over T-cell selectivity. Its pyridyl analogue 4 was found to be a highly potent and selective B-cell immunosuppressant with a 75-fold selectivity for B- over T-cells (as judged by the MLR data) and no general cytotoxicity at concentrations up to 160-fold higher than those required to inhibit B-cells. In the mouse, 4 effectively blocked TI-1 Ab production and suppressed Ab-mediated xenograft rejection in a xenotransplantation model under a once-daily dosing regimen, with efficacy down to 0.3 mg/kg/day po. These are the first data demonstrating the feasibility of the development of drugs specific for impeding Ab production.

Animals↗
PubMed1999

Verruciform xanthoma of the nose.

We report a case of verruciform xanthoma of the nasal skin. The case is unique because the lesion both bled and has shown evidence of multicentricity.

Adult↗
PubMed1996

The taste of monosodium glutamate: membrane receptors in taste buds.

Receptor proteins for photoreception have been studied for several decades. More recently, putative receptors for olfaction have been isolated and characterized. In contrast, no receptors for taste have been identified yet by molecular cloning. This report describes experiments aimed at identifying a receptor responsible for the taste of monosodium glutamate (MSG). Using reverse transcriptase (RT)-PCR, we found that several ionotropic glutamate receptors are present in rat lingual tissues. However, these receptors also could be detected in lingual tissue devoid of taste buds. On the other hand, RT-PCR and RNase protection assays indicated that a G-protein-coupled metabotropic glutamate receptor, mGluR4, also is expressed in lingual tissues and is limited only to taste buds. In situ hybridization demonstrated that mGluR4 is detectable in 40-70% of vallate and foliate taste buds but not in surrounding nonsensory epithelium, confirming the localization of this metabotropic receptor to gustatory cells. Expression of mGluR4 in taste buds is higher in preweaning rats compared with adult rats. This may correspond to the known higher sensitivity to the taste of MSG in juvenile rodents. Finally, behavioral studies have indicated that MSG and L-2-amino-4-phosphonobutyrate (L-AP4), a ligand for mGluR4, elicit similar tastes in rats. We conclude that mGluR4 may be a chemosensory receptor responsible, in part, for the taste of MSG.

Amino Acid Sequence↗
PubMed1995

[Severe pulmonary and meningeal cryptococcosis in an immunocompetent Cambodian].

A chest x-ray showing a large tumor-like opacity in the left lower lobe and endoscopy visualizing a budding mass suggested a diagnosis of bronchial carcinoma in a 55-year old, tobacco-smoking Cambodian who consulted for hemoptysis and altered general status. Histological study of bronchial biopsies allowed differential diagnosis of cryptococcosis. Serologic tests for human immunodeficiency virus were negative and there was no other cause of immunodepression. Left lower lobectomy was performed at the German hospital of the APRONUC in Phnom Penh. Examination of the surgical specimen confirmed massive bronchopulmonary cryptococcosis. Two months after the procedure the patient was readmitted for neuromeningial cryptococcosis that responded well to fluconazole. Another relapse occurred 5 months later and was treated using the same drug. The patient is currently in remission. An increasingly common deep mycosis that is serious but curable with proper treatment, cryptococcosis deserves the full attention of physicians working in Cambodia where, as in other tropical zones, it is likely that this infection will progress with the incidence of AIDS. Symptoms can be misleading, suggesting neuromeningial or pulmonary tuberculosis. The value of India ink smear which should be performed in all patients presenting lymphocytic meningitis with hypoglycorrhachia must be emphasized. In the present case bronchoscopy was useful to distinguish from bronchopulmonary cancer.

Cambodia↗
PubMed1995

Mastoiditis in Kelantan.

Chronic mastoiditis and subperiosteal abscess are rarely seen nowadays in most countries. Thirty-four cases of mastoiditis were reviewed to find out the prevalence of chronic mastoiditis in the east coast of Malaysia. Twenty (58.82%) of these cases were a sequelae of chronic suppurative otitis media with cholesteatoma. All the patients with chronic mastoiditis were more than six years old. Forty-five percent of cases with chronic mastoiditis had a well pneumatized mastoid air cell on the unaffected side. The occurrence of chronic mastoiditis or cholesteatoma in a well pneumatized mastoid is not really as rare as was thought to be. X-ray of the mastoids is very useful in diagnosing patients with chronic mastoiditis and cholesteatoma. Mastoiditis is uncommon in adults and whenever a case is seen, an underlying pathology like cholesteatoma should be suspected.

Adolescent↗
PubMed1993

Urinary fibrin (-ogen) degradation products in Russell's viper (Daboia russelii siamensis) bite victims.

Serum and urine concentrations of fibrin (-ogen) degradation products (FDP) were estimated in 20 proven Russell's viper bite (RVB) cases with severe defribination. All patients had similar degrees of high serum FDP levels. However, the ten who developed into acute renal failure (ARF) had significantly (p < 0.001) higher urinary FDP levels than those who did not. The urinary FDP levels of ARF cases increased correspondingly with high serum FDP levels but not in cases without ARF. Serial comparison of serum and urinary FDP levels in RVB cases with severe defibrination may be of value in predicting the likelihood of developing ARF. The present study favored disseminated intravascular coagulation as the main cause of ARF in Myanmar RVB cases.

Fibrin Fibrinogen Degradation Products↗
PubMed1989

The action of Russell's viper venom on fibrin formation and fibrinolysis in vivo.

Envenoming by Russell's viper caused a marked rise in FPA, B beta 15-42 fragment and fibrin derived cross-linked D-dimer fragment indicative of a consumptive coagulopathy with hyperfibrinolysis. There was no increase in tPA or tPA-I levels post envenoming, which suggests that the increase in fibrinolytic activity was not due to venom-induced release of tPA from the vessel walls but may have been attributable to a direct effect of the venom or to a secondary physiological response to fibrin deposition. The effectiveness of the antivenom is demonstrated by its ability to prevent further cleavage of fibrinogen and the return to normal fibrinogen levels by 24 h. A secondary rise in FPA at this time indicates that the initial dose of antivenom may have been too small. The antivenom alone or in combination with the venom causes the release of tPA, tPA-I and vWF by the vessel walls. This may be a consequence of the severe anaphylactic reactions seen in some patients.

Adolescent↗
PubMed1987

Human cerebral malaria: a pathological study.

The following report using light and electron microscopic and immunological techniques is based on a series of 19 Burmese patients who died of cerebral malaria. The principal change was blockage of cerebral capillaries by Plasmodium falciparum-infected erythrocytes. Ring hemorrhages and segmental necrosis of cerebral capillaries were common. Cerebral edema was variable in these cases. Electron-dense knobs, 40 X 80 nm in size, which protruded from the membrane of infected erythrocytes, formed focal junctions between endothelial cells and erythrocytes. These junctions resulted in the entrapment of erythrocytes and caused blockage in the capillary lumen. Immunoperoxidase study revealed that P. falciparum antigens and IgG deposits in the capillary basement membrane. This implies that damage to the cerebral capillary could be related to immune mechanisms.

Adolescent↗
PubMed1979

Rupture strength of skin wounds in jaundiced rats.

The rupture strength of 7-day-old wounds in normal rats, in rats in which there had been a previous skin incision, and in sham bile-duct-ligated and bile-duct-ligated jaundiced groups of rats was studied. It was found that wounds in jaundiced rats were significantly weaker than the wounds in the normal group of rats. Skin wounds in normal animals were significantly stronger than wounds in animals with sham bile-duct ligation. No difference was seen between sham bile-duct-ligated and bile-duct-ligated jaundiced rats.

Animals↗