Class I major histocompatibility complex antigen disparity is not a barrier to successful pancreatic islet cell engraftment.
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Biomedical subjects
Publications and source records attributed to K Jain.
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Disorders of fatty acid beta-oxidation have been suggested as playing a significant role in the sudden infant death syndrome (SIDS). To elucidate the role of medium-chain acyl-coenzyme A dehydrogenase (MCAD) deficiency in SIDS, we identified all cases of SIDS occurring in Los Angeles County between January 1986 through December 1991. A total of 1304 SIDS deaths were identified; tissue samples were collected in 1236 cases (94.8%). Extraction of DNA was successful in 1224 tissue samples (93.9%), which were examined for the presence of the G985 mutation, identified as occurring in more than 88% of affected cases of MCAD deficiency. Three heterozygotes and no homozygotes were identified; this incidence does not differ from that reported in the general population. Review of the pathologic specimens from the identified heterozygotes and from 18 ethnic-, age-, and sex-matched control subjects revealed significant fatty infiltration of all organs examined in one of the three heterozygotes and in none of the control subjects. We conclude that MCAD deficiency does not play a significant role in the causation of SIDS.
We investigated the effects of the thrombin inhibitor, argatroban ((2R,4R)-4-methyl-1-[N2-(3-methyl-1,2,3,4-tetrahydro-8- quinolinesulfonyl)-L-arginyl]-2-piperidinecarboxylic acid) on the endothelium-derived relaxing factor-nitric oxide (EDRF-NO)-dependent relaxant, and the endothelial cell-independent constrictor actions of thrombin. Experiments were performed in isolated rings of canine coronary arteries. Argatroban inhibited thrombin-induced relaxation (range of thrombin activity 0.003-0.3 U/ml), with an ED50 of 0.3 microM. The ED50 value was not different from inhibition of thrombin amidolytic cleavage of the chromogenic substrate N-p-tosylgly-pro-arg-p-nitroanilide acetate (TOGSPAN 0.28 microM), but inhibition was highly selective. Argatroban did not block EDRF-NO-dependent relaxations to trypsin (0.003-0.3 U/ml; Emax -88.7 + 2.0% without vs. -88.1 +/- 2.7% with argatroban), acetylcholine (ACh 1 nM to 1 microM; Emax -90.5 +/- 4.7% and -88.6 +/- 3.1%, with and without argatroban, respectively), or the calcium ionophore A23187 (1 nM to 1 microM; Emax -98.5 +/- 1.2 vs. -99.4 +/- 0.6%). The inhibitory effects of argatroban on thrombin-induced constriction were then compared with those of the irreversible thrombin inhibitor D-phenylalanyl-L-prolyl L-arginine chloromethyl ketone (PPACK). The highest concentration of argatroban (10 microM) inhibited the vasoconstrictor effects of thrombin but did not completely block the effects (Emax 21.4 +/- 8.1% of KCl constriction without argatroban and Emax 14.0 +/- 5.2% of KCl-induced constriction with argatroban). In contrast, both a 10- and a 100-fold lower concentration of PPACK (0.1-1 microM) prevented the thrombin-induced increase in tension. Thrombin-induced constriction therefore appeared to disclose mechanistic differences between the two thrombin inhibitors. Thrombin vasomotor actions were inhibited by argatroban, however, and this may contribute significantly to the therapeutic effect of argatroban.
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OBJECTIVE--To assess the efficiency, reliability, and ease of use of DNA diagnosis for Duchenne and Becker muscular dystrophies (DMD/BMD) using the polymerase chain reaction (PCR). DESIGN--DNA from the patients was screened for deletion mutations using multiplex PCR, and the results were compared with those obtained by Southern blot analysis. The PCR multiplex reaction detects nine specific "hot-spot" exons in the dystrophin gene while the Southern analysis detects 66 specific dystrophin gene restriction fragments. The multiplex reaction requires 50-fold less DNA than Southern analysis and thus is considerably more sensitive. SETTING--Fourteen university-affiliated and private genetic disease diagnostic laboratories. PATIENTS--Male patients with clinical signs of DMD/BMD. Cases were selected for analysis randomly, without knowledge of whether a deletion was present within the dystrophin gene. MAIN OUTCOME MEASURES--The percentage of cases that were detectable by multiplex PCR in comparison with Southern analysis, the frequency, extent, and location of the detected deletion mutations. In some cases, duplication mutations were monitored. RESULTS--The accuracy of a single PCR multiplex amplification (nine exons) was compared with Southern analysis with 10 cDNA probes that cover the full length of the gene. The multiplex PCR analytic method detected 82% of those deletions detected by Southern analysis methods. In one of 745 analyses, the multiplex method suggested a single exon deletion, which was not confirmed by Southern analysis, representing a false-positive rate of 0.013%. CONCLUSIONS--Multiplex PCR represents a sensitive and accurate method for deletion detection of 46% of all cases of DMD/BMD. The method requires 1 day for analysis, is easy to perform, and does not use radioactive tracers. As such, multiplex PCR represents an efficient and rapid method for prenatal or postnatal diagnosis of DMD/BMD.
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Angiomyolipoma is an uncommon benign tumour accounting for less than 1% of all surgically excised tumours of the kidney. It may present as an isolated lesion or in association with tuberous sclerosis. An impalpable tumour is often detected incidentally during investigation of a case for some urinary tract pathology. CT scan has proved to be a useful investigation for pre-operative diagnosis; it may however, be of no value if the fat content of the tumour is low. Here a case of angiomyolipoma of left kidney is reported where pre-operative diagnosis was suggested by CT scan and histopathology confirmed it.
The leaf-hopper P. pictus is a well-known pest of Calotropis plants. Adult females and males were treated with a sublethal BHC concentration to control fecundity and viability. Marked histological changes occurred in the follicular epithelium of both pathological and immature oocytes. Vitellogenesis was completely arrested and the PYP bodies present prior to treatment disintegrated and were resorbed by the pycnotic follicular epithelium. Fibrogenesis and thickening of the tunica propria gradually decreased. The sublethal BHC concentration injected into the haemolymph severely damaged the fat bodies and thus adversely affected the developing ovaries. When adults were treated and kept in separate pairs, mating was prolonged; it was followed by ovulation, but the number of eggs was always smaller than in the control females and they did not develop any further, although provided in the laboratory with all normal conditions.
Cockroaches are familiar pests of grain stores. They are prolific breeders and can also transmit various diseases. Adult females were therefore treated with sublethal BHC and DDT concentrations to control their fecundity and viability. Ovulation was arrested as a result of damage to and resorption of the terminal oocytes. Histopathological changes were clearly expressed in the follicular epithelium of pathological oocytes and also in immature oocytes. Vitellogenesis was arrested and protein yolk precursors were broken down and destroyed by the pycnotic follicular epithelium. Fibrosis and thickening of the tunica propria gradually diminished. Prolonged treatment resulted in atrophy of the ovaries, together with a large number of immature and pathological oocytes. Since the effect of DDT is cumulative, the histopathological changes it caused were severer than those induced by BHC. Treated adults kept in pairs showed prolonged duration of mating, followed by a 2-3 days' delay in ootheca formation; no first instar nymphs emerged from these oothecae, however, owing to the failure of fertilized eggs to develop any further in the oothecal lumen.
Endogenous aspergillus endophthalmitis is not a common entity. So far, about 25 cases have been reported in the world literature, and to the best of our-knowledge, the crystalline lens was invaded by the fungus in none of the cases, as seen in the present case. This unusual feature, coupled with the rarity of the condition in general, made it worth reporting.
Fifty-eight patients of interstitial lung diseases and 30 control patients were submitted to bronchoalveolar lavage (BAL) with flexible fibreoptic bronchoscopy. In 30 controls (with fluid recovery 61.7%) total cell count was 175 +/- 31/mm3 with macrophages 87.5 +/- 2.0%, neutrophils 7 +/- 1.9 and lymphocytes 5 +/- 0.6%. In idiopathic interstitial fibrosis (34 cases) these values were respectively 832 +/- 221/mm3, 47 +/- 5.5, 29 +/- 5.0 and 19 +/- 5 percent (significantly different P: less than 0.005, 0.001, 0.1 and 0.005 respectively from control. The results of bilateral lavages in 28 interstitial cases were similar. In other categories viz: sarcoidosis(8), macrophages were significantly fewer (61 +/- 10%: P less than 0.05) and lymphocytes significantly more (27 +/- 6.4%: P less than 0.05); in rheumatoid lung disease (4 cases) significantly fewer macrophages (45 +/- 5) were seen and 12 cases with methyl isocyanate exposure showed insignificant changes.
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The success of autologous bone marrow transplantation for B cell lymphoma may depend on the efficacy of in vitro purification of patients' tumor cell-contaminated marrow. In this study, we tested the toxicity of seven different chemotherapeutic agents against two B cell lymphoma lines (LY-16 and SK-DHL-2) as compared to normal human bone marrow granulocyte-macrophage progenitor cells (CFU-GM). 4-Hydroperoxycyclophosphamide (4-HC), VP-16-213 (VP-16), nitrogen mustard, and vincristine showed a highly selective toxicity against cultured lymphoma cells; i.e., at doses sufficient to induce a 4-log clonogenic tumor cell reduction (4-HC 21 micrograms/ml, VP-16 50 micrograms/ml, nitrogen mustard and vincristine 5 micrograms/ml), 10.0 +/- 6.7, 3.0 +/- 3.2, 23.2 +/- 22.7 and 24.0 +/- 17.0% (mean +/- 1 SD), respectively, of normal bone marrow CFU-GM were preserved. The differential sensitivity of tumor cells and normal hematopoietic precursors was less prominent after exposure of cells to cis-diamminechloroplatinum II (cis-platinum); thus, at a drug dose of 100 micrograms/ml, all detectable lymphoma cells could be eradicated (i.e., greater than or equal to 4 log reduction) while a CFU-GM recovery of only 0.2 +/- 0.2% was observed. In contrast, adriamycin and bleomycin, at the highest tumoricidal concentrations tested (5 and 100 micrograms/ml, respectively) did not exhibit a selective toxicity toward lymphoma cell lines. In summary, our results suggest that nitrogen mustard and vincristine, as well as 4-HC and VP-16, may be useful agents for the ex vivo treatment of bone marrow grafts form B cell lymphoma patients.
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A 32 year old male Hindu, presenting with generalized muscular hypertrophy (Veritable Hercules), together with subcutaneous nodules and epilepsy, due to cysticercosis is described.