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Biomedical subjects

R Jain

Publications and source records attributed to R Jain.

At least 55 records · Page 3Linked to original sources

Using an in vivo phagemid system to identify non-compatible loxP sequences.

The site-specific recombination system of bacteriophage P1 is composed of the Cre recombinase that recognizes a 34-bp loxP site. The Cre/loxP system has been extensively used to manipulate eukaryotic genomes for functional genomic investigations. The creation of additional heterologous loxP sequences potentially expands the utility of this system, but only if these loxP sequences do not recombine with one another. We have developed a stringent in vivo assay to examine the degree of recombination between all combinations of each previously published heterologous loxP sequence. As expected, homologous loxP sequences efficiently underwent Cre-mediated recombination. However, many of the heterologous loxP pairs were able to support recombination with rates varying from 5 to 100%. Some of these loxP sequences have previously been reported to be non-compatible with one another. Our study also confirmed other heterologous loxP pairs that had previously been shown to be non-compatible, as well as defined additional combinations that could be used in designing new recombination vectors.

Attachment Sites, Microbiological↗

Regiospecific synthesis of 2,3-disubstituted-L-histidines and histamines.

Regiospecific synthesis of 2,3-disubstituted-L-histidines and 2,3-disubstituted histamines starting from L-histidine methyl ester and histamine is reported. The key step involves homolytic free radical alkylation via silver catalyzed oxidative decarboxylation of alkylcarboxylic acids with ammonium persulfate.

Alkylation↗

Hydrops fetalis in an interstitial deletion of chromosome 10.

We report the case of a premature neonate with ascites and dysmorphic facial features at birth. The chromosomal analysis showed an interstitial deletion of chromosome 10, that is, 46, XX, del(10)(q22.3q24.1). This is the first known case of a patient with interstitial deletion of chromosome 10 with symptoms of ascites and hydrops.

Chromosome Banding↗

A fluorescence-based homogeneous assay for measuring activity of UDP-3-O-(R-3-hydroxymyristoyl)-N-acetylglucosamine deacetylase.

UDP-3-O-(R-3-hydroxymyristoyl)-N-acetylglucosamine deacetylase (LpxC) is one of the key enzymes of bacterial lipid A biosynthesis, catalyzing the removal of the N-acetyl group of UDP-3-O-(R-3-hydroxymyristoyl)-N-acetylglucosamine. The lpxC gene is essential in Gram-negative bacteria but absent from mammalian genomes, making it an attractive target for antibacterial drug discovery. Current assay methods for LpxC are not suitable for high throughput screening, since they require multiple product separation steps and the use of radioactively labeled material that is difficult to prepare. A homogeneous fluorescence-based assay was developed that uses UDP-3-O-(N-hexyl-propionamide)-N-acetylglucosamine as a surrogate substrate. This surrogate can be prepared from commercially available UDP-GlcNAc by enzymatic conversion to UDP-MurNAc, which is then chemically coupled to n-hexylamine. Following the LpxC reaction, the free amine of the deacetylation product can be derivatized by fluorescamine, thus generating a fluorescent signal. This surrogate substrate has a K(m) of 367 microM and k(cat) of 0.36 s(-1), compared to 2 microM and 1.5 s(-1) for the natural substrate. Since no separation is needed, the assay is easily adaptable to high throughput screening. IC(50)s of LpxC inhibitors determined using this assay method is similar to those measured by traditional method with the natural substrate.

Amidohydrolases↗

MR spectrum in spinal dysraphism.

Spinal dysraphism is a general term which encompasses a wide variety of anomalies of the spine, all of which result from imperfect midline fusion of the embryonic neural tube. This term refers to large defects that involve the spine and not to small vertical clefts commonly seen within the spinal process of L5 or S1. We present a spectrum of MR imaging findings selected from a retrospective review of 100 patients of spinal dysraphism evaluated at our institution.

Diagnosis, Differential↗

Intraspinal neurenteric cysts--report of three paediatric cases.

BACKGROUND: Neurenteric cysts are rare congenital lesions of the spine and are lined with entodermal epithelium. They result from anomalous endodermal-neuroectodermal adhesion in the 3rd week of embryonic life with persistence of canal of Kovalevsky. The nature of the eventual abnormality depends on the extent to which this adhesion subsequently disappears. Persistence of the entire tract results in the extreme form of combined anterior and posterior spina bifida with dorsal enteric fistula and persistence of only a part of the tract producing the isolated intraspinal cyst. The most common location is the cervico-dorsal region, and usually it lies ventral to the spinal cord. The lumbosacral location is uncommon. Associated vertebral anomalies, gut cysts, bowel duplication, the presence of keratin markers and mucin-secreting cuboidal or columnar intestinal epithelium in their walls confirm their entodermal origin. PATIENTS: We describe here three unusual cases of neurenteric cysts in patients aged 5-18 years who had already had symptoms for some time. One of these had a cyst sited predominantly in the sacral canal, another presented with a lumbar neurenteric cyst, and the third patient had an intradural extramedullary thoracic lesion. Two of these children had associated anomalies, the one with lumbar cyst also having a lipomeningomyelocele and spina bifida while the other also had deformed vertebrae. All three patients underwent laminectomy and gross excision of the cysts through a posterior approach. RESULTS AND CONCLUSION: The diagnosis of neurenteric cysts was confirmed by demonstrating mucin-producing cuboidal or columnar epithelium lining the cystic cavity.

Adolescent↗

Safety and efficacy of AS-1 red blood cell use in neonates.

Many Regional Blood Centers are providing AS-1(Adsol preservative) red blood cells (RBCs) as a standard product because of the extended shelf life (42 days). The use of AS-1 RBCs is concerning in neonates because of high exposure to dextrose, adenine and mannitol. We conducted this study to evaluate the safety and efficacy of AS-1 RBC use in neonates. We assigned one unit of AS-1 RBCs to each infant for small volume transfusions (15 ml/kg) for the life of the unit (42 days). The study was conducted for one year. The infants under 1500 g were included in the study. We measured the pre- and post-transfusion hematocrit, post-transfusion serum sodium, potassium, glucose, bilirubin and blood pH. We compared the average number of transfusions per patient and average blood donor exposure per patient using AS-1 RBC to CPDA-1 packed red blood cells (PRBC) use, data available for prior year. We monitored the blood transfusion reactions during the study period. The hematocrit increased significantly from 30.1 +/- 4.6 pre-transfusion to 38.3 +/- 4.9 post-transfusion. The post-transfusion serum bilirubin, blood pH, serum potassium, sodium and glucose remained within the normal range. In spite of an increase in the number of average transfusions per patient with AS-1 RBC (6.67 +/- 5.1), the average donor exposure (1.8 +/- 1.1) remained less than two donors. There were not any transfusion reactions reported during the study. In conclusion, the use of AS-1 red blood cells is safe for small volume transfusions in neonates.

Adenine↗

Ischaemic heart disease may predispose to pseudophakic cystoid macular oedema.

PURPOSE: Pseudophakic macular oedema (PMO) is uncommon following uncomplicated phacoemulsification and lens implantation and the cause of infrequent cases is rarely understood. This study was undertaken to determine whether a relationship exists between ischaemic heart disease (IHD) and PMO. METHODS: Retrospective case note review was carried out of 177 (252 eyes) consecutive patients without pre-existing retinal disease who underwent phacoemulsification and intraocular lens implantation during a 12 month period. Patients with a post-operative best corrected visual acuity < 6/9 underwent slit-lamp biomicroscopy and fluorescein angiography to identify PMO. IHD was defined on clinical and electrocardiographic grounds. The incidence of IHD was compared in patients with and without PMO and statistical analysis performed using the Fisher's exact test. RESULTS: PMO occurred in 4 patients (6 eyes), all of whom had IHD, whereas no PMO occurred in the remaining 173 patients (246 eyes) (p = 0.04). CONCLUSIONS: Pseudophakic macular oedema represents an important complication following modern phacoemulsification and intraocular lens implantation and is associated significantly with ischaemic heart disease.

Aged↗

Fracture of lower femoral epiphysis in an infant at birth: a rare obstetrical injury.

We report a case of rare birth injury leading to physeal fracture after a routine cesarean delivery. Because plain radiographics are often normal, therefore these physeal fractures usually present a diagnostic challenge in the newborn. In this case, ultrasonography and magnetic resonance imaging were helpful in making an early accurate diagnosis. The infant received prompt treatment and the physeal fracture healed uneventfully. Physeal fractures should be included in the birth injuries following routine cesarean delivery.

Adult↗

Intra-arterial embolization of lumbar artery pseudoaneurysm following percutaneous nephrolithotomy.

The management of a patient with haematuria following percutaneous nephrolithotomy is described. The patient underwent renal angiography to assess the cause of bleeding. A pseudoaneurysm arising from first left lumbar artery was incidentally discovered, which was then successfully embolized using an indigenously fabricated metallic coil and gel foam particles in the same sitting.

Aneurysm, False↗

Tolerability and pharmacokinetics of the collagenase-selective inhibitor Trocade in patients with rheumatoid arthritis.

OBJECTIVES: The purpose of this study was to assess the tolerability and multiple-dose pharmacokinetics of Trocade in rheumatoid arthritis patients. METHODS: Forty-eight patients entered this double-blind, placebo-controlled, multiple ascending dose study. Patients received Trocade (25, 50, 100 or 150 mg) or placebo once daily for 28 days. Tolerability was assessed daily. Plasma pharmacokinetics was assessed on days 1 and 28. Trough blood samples were collected weekly. RESULTS: Trocade was well tolerated, with no differences in the adverse event profile compared with placebo. There were no relevant changes in laboratory parameters, vital signs or 12-lead ECG recordings. Plasma concentration profiles showed that Trocade was rapidly absorbed and most was eliminated within 24 h. The area under the plasma concentration-time curve and the maximum plasma concentration reached increased with dose, but this increase was not proportional to dose. No relevant accumulation was seen. CONCLUSIONS: Trocade was well tolerated for the 28-day study period. From exposure data, doses of 100 and 150 mg were expected to yield plasma levels associated with efficacy, and from trough concentrations the doses of 25 and 50 mg were also expected to be efficacious.

Adult↗

An experimental study of tolerance among alcohol dependent individuals.

BACKGROUND & OBJECTIVES: Continued alcohol use leads to tolerance, however, some dependent individuals lose tolerance despite continued alcohol consumption. The exact mechanism for this is not known. This study evaluated tolerance in alcohol dependent patients in a treatment centre using multiple measures. METHODS: Male patients with alcohol dependence (DSM III R criteria) were chosen and detoxified in an inpatient setting. On day 14 of detoxification, each subject was given ethanol (0.75 g/kg body wt) mixed in an equal amount of placebo (cola) drink once and an equivalent amount of placebo (cola) during the other occasion in a single blind, randomised, cross over manner. Assessment of each subject was made using multiple measures (clinical, neuro-psychological tests, scales for subjective effect and blood alcohol levels), 30 min after intake of each drink. RESULTS: The subjects (n = 26) did not very under the two conditions (alcohol/placebo) as regards subjective effects, tests on logical memory and Bender Gestalt test (BGT). Cognitive screening scores though different under the two conditions, were within the normative range. Of these 26 subjects, 50 per cent showed clinical signs of intoxication after consumption of alcohol. These two groups (impaired vs unimpaired) were comparable on all base-line clinical parameters, assessment of euphoria and sedation, and various neuropsychological tests except BGT under the two conditions (placebo/alcohol). The non-tolerant (impaired) group scored significantly (P < 0.05) worse on BGT after alcohol consumption. INTERPRETATION & CONCLUSIONS: The study suggests that clinical tests were more sensitive in detecting intoxication. Further studies are needed to understand the mechanism of loss of tolerance.

Adolescent↗

Abuse liability of diazepam through different routes.

Abuse liability of diazepam was examined among experienced drug users. The subjects, randomly divided into two groups, each having eight subjects, received diazepam, 15 mg intravenously (gr. 1) and 30 mg orally (gr. 2). Subjective states, drug liking, sedation and euphoria were assessed at pre-drug, 15 min, 120 min and 240 min post-drug administration. In addition, brief assessment to evaluate euphoria and sedation was carried out at 5 min and 45 min for subjects in gr. 1, and at 45 min and 150 min for those in gr. 2. Plasma diazepam level was also estimated. Results indicate those subjects in gr. 1 reported quicker and higher euphoria, drug liking, subjective effects and higher plasma level. The study suggests that route of administration of a compound which has faster onset of action is associated with more liability of abuse.

Adult↗

Acute disseminated encephalomyelitis--another cause of post malaria cerebellar ataxia.

The aetio-pathogenesis of delayed onset cerebellar ataxia following Plasmodium falciparum malaria is uncertain. An autoimmune demyelinating pathology has been suspected though not yet definitively substantiated. In the present communication we report a case of delayed onset cerebellar ataxia following acute falciparum malaria, where magnetic resonance imaging revealed demyelinating lesions in the pons and cerebellar peduncles which disappeared after resolution of symptoms.

Acute Disease↗