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Biomedical subjects

K Amin

Publications and source records attributed to K Amin.

51 records · Page 3Linked to original sources

Binding of Galanthus nivalis lectin to Chlamydia trachomatis and inhibition of in vitro infection.

A glycoprotein present in Chlamydia trachomatis, serotype L1, elementary bodies (EBs) was earlier found to bind the lectin from Galanthus nivalis (GNA). In the present paper we investigate the interaction of GNA with chlamydial EBs and its effect on in vitro infectivity. The binding affinity was studied with 125I-GNA lectin. Within 15 min about 80% maximal binding was obtained. The chlamydia-GNA interaction was inhibited by alpha-methylmannoside, causing a decrease of about 50% at 1 mM. Curve fit analyses indicated two types of binding sites for GNA on the EBs. The affinity to these differed by a factor of 15. The influence of the lectin on the ability of C. trachomatis to infect McCoy cells was also investigated. There was a GNA-dependent inhibition with a 50% reduction in the number of intracellular inclusions at 0.2 microM of the lectin. The findings indicate the presence of terminal mannose structures on the chlamydial surface at or in the proximity of the cell-binding domains. Mannose-binding proteins of eukaryotic cells could be important for the initial uptake of EBs.

Animals↗

Binding of type-I collagen to Chlamydia trachomatis.

Denatured type-I collagen was found to bind to Chlamydia trachomatis elementary bodies (EBs) in a time-dependent and specific manner. Specificity was tested by having a large excess of other proteins present in the binding mixture. Only denatured type-I collagen efficiently competed for binding. Radiolabelled fibronectin did not bind under the test conditions used. The binding was temperature-dependent and the interaction increased at the melting temperature of the collagen. Evidence was found for two binding sites: one with high affinity (Kd 3.3 x 10(-9)) and one with low affinity (Kd 1.7 x 10(-7)), with an estimated number of binding sites per EB of 590 and 2900, respectively. The interaction between C. trachomatis and collagen may also be relevant in vivo, since 50% binding occurred at 37 degrees C. The binding to denatured collagen may be of importance for the development of sexually acquired reactive arthritis.

Animals↗

Borrelia burgdorferi reactivity in patients with severe persistent fatigue who are from a region in which Lyme disease is endemic.

Borrelia burgdorferi is the pathogen that causes Lyme disease. Patients frequently experience fatigue and malaise that can persist after antibiotic treatment. This study examined serological reactivity to B. burgdorferi in patients with chronic fatigue who were from a region in which Lyme disease is endemic. Blood and CSF were collected from patients without a history of infection due to B. burgdorferi (n = 12) and patients with persistent fatigue after antibiotic treatment of Lyme disease (n = 13). Serum and CSF were examined by ELISA for antibodies to B. burgdorferi, and routine studies of CSF were done. In the first group, one patient (8%) was seropositive; no patients had detectable antibodies in CSF. In the second group, nine patients (69%) were seropositive or borderline seropositive; seven (54%) had detectable antibodies in CSF. Unexplained abnormalities in CSF were noted in 42% and 31% of patients in each group, respectively. In this study positive serologies for Lyme disease were not found at a higher than expected rate for patients from a region of Lyme disease endemicity who had idiopathic chronic fatigue. Fatigued patients did show a surprisingly high rate of unexplained minor CSF abnormalities suggestive of CNS or meningeal dysfunction.

Adolescent↗

Digit Memory Test: unequivocal cerebral dysfunction and suspected malingering.

The Digit Memory Test (DMT) (Hiscock & Hiscock, 1989), a forced-choice test for detecting malingering, was administered to 27 patients with unequivocal cerebral dysfunction, 5 patients with postconcussional syndrome, 6 suspected malingerers and 10 normal controls. Results indicate that, even in patients with severe, but static cerebral dysfunction and unequivocal memory disorder, DMT performance is between 95% to 100% correct. By contrast, the 6 patients in whom malingering was seriously considered performed at a level much below the other three groups (74% correct) but not significantly below chance. The DMT may be helpful in evaluating patients suspected of malingering even when they do not score significantly below chance.

Adult↗

Pleuritis as a manifestation of reactivation tuberculosis.

PURPOSE: The purpose of this study was to determine the frequency with which tuberculous pleuritis is a manifestation of reactivation tuberculosis and to compare the clinical manifestations of reactivation tuberculous pleuritis with "classic" tuberculous pleuritis, in which chest roentgenograms reveal no parenchymal infiltrates. PATIENTS AND METHODS: We evaluated the medical records of 59 patients in whom tuberculous pleuritis was confirmed by histologic findings or mycobacterial culture. Twenty-seven patients (46%) had typical chest roentgenographic findings of reactivation tuberculosis, whereas 32 (54%) had classic tuberculous pleuritis. The clinical and laboratory features of these two groups were compared. RESULTS: Symptoms were more prolonged and pleural fluid glucose and lactate dehydrogenase concentrations were more markedly abnormal in patients with reactivation pleuritis than in those with classic pleuritis, suggesting a more chronic inflammatory process in the former group. Compared with patients with classic tuberculous pleuritis, those with reactivation pleuritis had a lower frequency of reactive tuberculin skin tests (61% versus 88%) and granulomatous pleural inflammation (25% versus 72%), but a higher bacillary burden, manifest by a higher frequency of positive sputum smears for acid-fast bacilli (50% versus 0%) and positive mycobacterial cultures from sputum (60% versus 23%) and pleural fluid (91% versus 66%). CONCLUSIONS: In contrast to previous reports, tuberculous pleuritis was a manifestation of reactivation tuberculosis in 46% (27 of 59) of patients. Tuberculous pleuritis is a more chronic process in patients with reactivation disease than in those with classic pleuritis. The lower frequency of reactive tuberculin skin tests and granuloma formation, combined with the higher bacillary burden in patients with reactivation pleuritis, suggest that these patients mount a less effective immune response to Mycobacterium tuberculosis infection than do patients with the classic form of tuberculous pleuritis.

Adult↗

Modulation of natural killer and antibody-dependent cellular cytotoxicity by interferon and interleukin-2 in chronic myeloid leukemia patients in remission.

Our earlier studies demonstrated that about 55% of chronic myeloid leukemia (CML) patients in remission exhibited impaired natural killer (NK) cytotoxicity (low NK responders) while antibody-dependent cellular cytotoxicity (ADCC) of these patients, on chicken red blood cells as targets, was within normal range. In this paper, we have attempted to modulate the NK cytotoxicity of CML patients in remission with interferon (IFN) and interleukin-2 (IL-2) singly or together. ADCC using K562 target-directed monoclonal antibody (MAb) 4.6E10 was also modulated by treating the effectors with IFN or IL-2. Pretreatment of nonadherent mononuclear cells from peripheral blood (NAPBMNC) with IFN or IL-2 was found to result in 20 and 21% increase in target cell lysis in case of healthy donors, 79 and 98% increase in case of CML normal NK responders, and 164 and 159% increase in case of CML low NK responders. Combined use of IFN and IL-2 potentiated further the lymphocytotoxicity to 25% in healthy donors, 135% in normal NK responder CML patients and 283% in low NK responder CML patients. This treatment resulted in restoration of cytotoxicity of the latter group of patients to a normal level. The augmentation was seen in 80-100% CML patients. Although ADCC with chicken red blood cells as targets was within normal range, ADCC mediated with MAb to K562 cells was significantly lower in CML low NK responders (24.5%) than CML normal NK responders (42.4%) and healthy donors (65.9%).(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Monoclonal↗

Dosage effects and individual responsivity to methylphenidate in attention deficit disorder.

Effects of three dosages of methylphenidate (0.15, 0.30 and 0.60 mg/kg) were assessed in 19 ADD-H children on a variety of cognitive, academic and behavioral measures in the laboratory and the classroom. A predominant linear pattern of improvement was found across almost all measures. A slight decrease between 0.3 and 0.6 mg/kg on one cognitive task leaves open the possibility that higher dosages reduce stimulant effectiveness or cause decrements on some kinds of "high-level/high load" tasks. Response patterns of individual children varied considerably across measures. All children improved on at least several measures. Results were interpreted as evidence for stimulant activation of self-regulatory processes.

Attention↗

Novel 'soft' anticholinergic agents.

The concepts involved in the design of 'soft' drugs (drugs which, after achieving their therapeutic role, are metabolised in a predictable manner and at a controlled rate to non-toxic moieties) have been further applied in the case of atropine. Selected aliphatic and cycloaliphatic esters of a hypothetical, inactive acidic metabolite of atropine were designed and found to have atropine-like activity, and to revert to the inactive metabolite in rat liver homogenates. Peak anticholinergic activity, measured by the degree of antagonism of carbachol-induced spasms of guinea pig ileum strips, was observed when the esters contained a quaternary group. The in vitro stability of the esters was determined in human plasma, in pH 12 buffer solution, and in rat liver homogenate; the fastest rate of hydrolysis occurred in rat liver homogenate, and least sterically hindered esters degraded more rapidly than hindered esters. Synthesis of the esters was achieved in two stages. Phenylmalonic acid and the appropriate alcohol gave phenylmalonic acid monoesters, which, after reaction with tropine, afforded the required diesters. The tertiary amine group on the tropine moiety of the diesters then allowed the preparation of quaternary derivatives.

Animals↗

The detection of enteropathogens in acute diarrhea in a family cohort population in rural Egypt.

In 8 villages of rural northeastern Egypt, a 2-year study of the etiologic agents associated with episodes of diarrhea was carried out. Stool specimens (3,243) from 3,513 episodes of diarrhea were processed for enteropathogens. The most commonly identified agents in the group with diarrhea were Giardia lamblia (44%), heat stable enterotoxin (ST)-producing enterotoxigenic Escherichia coli (ETEC) (15%), heat labile toxin (LT)-producing ETEC (12%), enteropathogenic E. coli (EPEC) (4%), rotavirus (3%), Shigella (2%) and Salmonella (1%). Isolation rates were increased in cases compared to controls for all agents except G. lamblia and EPEC strains. Rotavirus, Salmonella and ST-producing ETEC were more frequently isolated during cooler months and Shigella and LT-ETEC occurred more commonly in warmer months. Campylobacter, EPEC, Giardia and E. histolytica did not show a discernable seasonal pattern. Rotavirus was primarily associated with diarrhea in infants only. Forty-four percent of children experienced at least 1 bout of rotavirus diarrhea by the age of 3 years. Vomiting was reported in 65% of cases of rotavirus infection. Dehydration was reported in greater than 40% of those with rotavirus-, Salmonella-, Campylobacter-, LT-ETEC- and EPEC-associated illness and in those without an identifiable agent. While rotavirus was implicated in 3% of cases overall, when vomiting or vomiting plus dehydration occurred, rotavirus was identified with a rate of 10% and 12%, respectively. Dysentery was common only in Shigella cases, occurring in 24%. A decrease in occurrence of rotavirus, Campylobacter and possibly EPEC illness was seen in the infants less than 6 months of age who were breast-fed when compared to those who were not.

Bacteria↗

Dissolution profiles for finely divided drug suspensions.

A suspension of micronized prednisolone acetate was separated into four fractions by the technique of centrifugal elutriation. Data showed that each fraction had a narrow particle size. The dissolution experiments were carried out under sink conditions (less than 10% of saturation concentration) in a dissolution apparatus with a rotating filter assembly and a continuous circulation of filtered fluid samples through a recording spectrophotometer. The dissolution profile was highly reproducible and substantially different for each fraction. As expected, fractions with the smallest and largest particles showed the fastest and slowest dissolution, respectively. Almost the entire dissolution profiles for four small particle size fractions can be satisfactorily described by the Higuchi-Hiestand model with the dissolution rate constant, K, in the range of 1.5-2.0 X 10(-9)cm2/sec. This is approximately 3.5 times greater than the value for K calculated on the basis of reported reasonable values for diffusion coefficient, density, and solubility.

Models, Theoretical↗

Suspending agent effects on steroid suspension dissolution profiles.

Dissolution profiles and particle-size analyses were determined for two lots of prednisolone acetate. The effects of common suspending agents on dissolution and particle-size distributions of these suspensions also were investigated. Lot-to-lot variation in the prednisolone acetate dissolution rate was observed and was apparently related to the percentage of fine particles within the distribution. Carboxymethylcellulose sodium inhibition of prednisolone acetate dissolution occurred with only one lot of raw material and seemed to be related to aggregation of the fine particles. Hydroxypropyl methylcellulose inhibited both prednisolone acetate lots and was observed with or without small particle aggregation. The dissolution variations observed have important implications in suspension formulation.

Excipients↗

Monocytes, but not macrophages, produce the eosinophil cationic protein.

The eosinophil cationic protein (ECP) is a cytotoxic protein with ribonuclease activity, produced and stored in bone marrow eosinophil myelocytes. Mature circulating eosinophils contain about 10 pg ECP per cell. The aim of this study was to investigate the possibility that monocytes produce and store ECP. By results from flow cytometry and specific protein measurement it is shown that human monocytes contain ECP (monocytes about 10 fg ECP per cell). RT-PCR analysis indicated the presence of mRNA coding for ECP in blood monocytes but not in alveolar macrophages. Furthermore, mRNA coding for ECP and low amounts of the protein were found in three myeloid cell lines representing different stages of monocytic differentiation. Differentiation of U-937 cells to macrophages induced lowered transcription of the ECP gene and reduced protein production. Immunohistochemical staining of lung tissue indicated that lung macrophages do not contain ECP. It is concluded that ECP is produced to a low extent by human monocytes and that the production is shut down during macrophage differentiation. This might indicate an alternative transcriptional regulation of the ECP gene in the monocytic lineage compared to the eosinophil lineage.

Antibodies, Monoclonal↗