Search PubMed⌕ Search

Biomedical subjects

K Prabhakaran

Publications and source records attributed to K Prabhakaran.

At least 91 records · Page 5Linked to original sources

Vasoactive intestinal peptide secreting tumours in children: a case report with literature review.

A 3 year old Chinese girl with watery diarrhoea, abdominal distension and hypokalaemia due to a thoracic paraspinal vasoactive intestinal peptide (VIP) secreting ganglioneuroma is reported. The pre-operative serum VIP was 314 pmol/l (normal less than 30). Her diarrhoea stopped after the removal of the tumour. The VIP was 14 pmol/l 6 months post-operatively. Review of the 19 reported cases in children with documented elevated serum VIP showed that many of the cases presented with watery diarrhoea for prolonged duration before the diagnosis was made. Earliest age of onset was 2 weeks of age. The male to female ratio was 9:10. Ganglioneuroma and ganglioneuroblastoma were the commonest tumours. Pancreatic non-beta cell hyperplasia and neurofibroma were also reported. Location of the tumour was variable: neck, chest or abdomen. Increased urinary catecholamine excretion was reported in 50% of the cases. Abdominal distension, flushing, episodic hypertension and failure to thrive were the other associated features.

Adenoma, Islet Cell↗

Beta-lactamase synthesis in Mycobacterium leprae.

Beta-lactam antibiotics are not active against Mycobacterium leprae. The enzyme beta-lactamase mediates the most common form of bacterial resistance to penicillins and cephalosporins. Cell-free extracts of purified suspensions of M. leprae were examined for beta-lactamase. The bacteria were prepared from the tissues of experimentally-infected nine-banded armadillos. Most of the suspensions were inactive. However, the bacteria obtained from the tissues of armadillos treated with penicillin G benzathine (bicillin) 6 months or more prior to sacrifice had beta-lactamase. If the organisms had been exposed to the antibiotic only for a few days, they were negative. Attempts to induce beta-lactamase in the bacteria in vitro did not succeed. Interestingly M. leprae separated from untreated armadillos, infected with the bacilli derived from treated animals contained the enzyme activity. Apparently, the M. leprae genome contains the operon for beta-lactamase, and once it is stimulated to express the enzyme, it continues to do so, even after the inducer is withdrawn.

Animals↗

Abdominal tuberculosis revisited.

Four patients with abdominal tuberculosis (ATB) managed in the University Department of Medicine, Singapore General Hospital, are presented to highlight problems encountered in the diagnosis of this condition. Three patients had intestinal tuberculosis, one of whom had peritoneal involvement and another had possible hepatic disease. The fourth patient presented with peritoneal disease alone. Ages at presentation ranged from 25 years to 71 years. There were three females and one male. Two patients presented with symptoms of chronic illness for 10 months before the disease was diagnosed. Two other patients had acute presentations. Fever, abdominal pain, vomiting and diarrhoea were the main symptoms encountered. Three patients had abdominal masses at diagnosis. Radiological investigations were the most useful diagnostic aid. Bacteriological confirmation was made in only one patient. Histology helped in the diagnosis in two others. Recent literature on this condition was reviewed and the possible role of impaired immunity in the pathogenesis of this condition was discussed.

Adult↗

Biochemical studies on Mycobacterium leprae.

Very little information is available on the basic biology of Mycobacterium leprae. It is not known why the organism fails to grow in bacteriological media or in cell cultures and why it has an unusual predilection for certain tissues in the human host where cells derived from the neural crest occur (e.g. skin, peripheral nerves, adrenal medulla). Biochemical studies have revealed that M. leprae contains an unusual form of the enzyme diphenoloxidase which has not been detected in other mycobacteria. The presence of a specific glutamic acid decarboxylase in the organism has been demonstrated. Although a few enzymes of glycolysis and tricarboxylic acid cycle have been investigated, nothing characteristic of the bacterium has been discovered, and how M. leprae derives energy for its survival and proliferation still remains obscure.

Alcohol Oxidoreductases↗

Canine orthotopic liver transplantation--is systemic veno-venous shunting necessary?

The experience of a single operating team performing the first 30 consecutive orthotopic liver transplants in dogs is reported. In 22 experiments during the anhepatic phase and as the liver graft is inserted in the recipient animal, the portal circulation is protected by a shunt to the jugular vein. Nine dogs survived 2-17 days. In 8 other unselected animals, both the portal vein and the infrahepatic vena cava were shunted to the jugular vein. Although blood pressure was better maintained in animals with 2 shunts, only one dog survived 10 days. Mention is also made of 11 subsequent transplant operations using a single porta-jugular shunt but reducing operating time by having 2 surgeons working on the donor and recipient animal simultaneously. Nine of the 11 dogs survived 2-6 days after the liver transplantation. The survival figures are comparable to those of other centres where double shunting is routinely performed. Our experience suggests that systemic veno-venous shunt may be omitted if the transplant procedure is performed expeditiously.

Animals↗

A possible metabolic role for o-diphenoloxidase in Mycobacterium leprae.

Among mycobacteria, Mycobacterium leprae is unique in its ability to oxidize a variety of diphenols to quinones in vitro. What physiologic role o-diphenoloxidase has in the organism remained unknown. Reducing substrates like NADPH, NADH and ascorbic acid reacted with the quinone formed from dopa (3,4-dihydroxyphenylalanine); the substrates were oxidized and the quinone was reduced back to diphenol in the process. Since the quinone undergoes reversible oxidation-reduction, diphenoloxidase might serve as an alternative respiratory mechanism in M. leprae for the utilization of other substrates, as has been reported in plants.

Animals↗

Temperature-induced changes in viability, diphenoloxidase and permeability of Mycobacterium leprae.

Among mycobacteria secretion of the enzyme diphenoloxidase has been established as a property of Mycobacterium leprae. The antileprosy drug dapsone (DDS), which completely inhibits the enzyme from plant and mammalian sources, does not readily penetrate intact M. leprae. When the drug is complexed with polylysine, it easily permeates the bacteria and produces 100% inhibition of its diphenoloxidase, suggesting a permeability barrier of the cytoplasmic membrane of M. leprae to dapsone. In this study: (1) when the organisms, purified from fresh tissues of experimentally infected armadillos, were treated with dilute alkali or exposed to warmer temperatures, DDS penetrated the bacteria and inhibited the diphenoloxidase. Washing with trypsin had no effect. Dapsone easily permeated the bacilli, purified from tissues stored at 0 degrees C or at -80 degrees C. (2) Diphenoloxidase of freshly-prepared M. leprae was stimulated when the bacteria were exposed to 50 degrees C for 10 min; at 60 degrees C the activity decreased, and at 100 degrees C the enzyme was completely inactivated. When the enzyme was assayed at temperatures below 37 degrees C, the activity was considerably lower, indicating that M. leprae may not be a psychrophilic organism in this respect. (3) The bacteria exposed to 50 degrees C failed to multiply in mouse footpads. M. leprae remained viable in tissues stored at 0 degrees C or -80 degrees C; but when the bacteria purified from these tissues were frozen, they lost their viability. On the other hand, the organisms separated from fresh tissues remained viable when frozen at -80 degrees C. The inhibition of diphenoloxidase of M. leprae by dapsone could serve as an indirect method to assess the integrity of the bacterial cell membrane and to predict whether the bacteria would retain their viability on freezing.

Catechol Oxidase↗

An alternative route for infecting armadillos with Mycobacterium leprae.

A nine-banded armadillo was inoculated with Mycobacterium leprae in both hind footpads. The animals were usually inoculated intravenously, or intradermally in the abdominal skin. Profuse multiplication of the bacilli occurred at the injection sites after more than two years. Eventually bacteraemia developed, and large numbers of the organisms were found in skin biopsies and in lymph nodes. There was limited dissemination of the bacteria into the spleen and the liver, and peripheral nerve invasion by the bacilli was also detected. M. leprae remained viable in the liver tissue, kept frozen at -80 degrees C for three years. This experimental system would be useful in testing the effects of certain immunological and chemotherapeutic agents against M. leprae by injecting them directly at the infection site.

Animals↗

Glutamic acid decarboxylase in Mycobacterium leprae.

Suspensions of Mycobacterium leprae purified from the organs (mostly spleen) of experimentally-infected armadillos (Dasypus novemcinctus, Linn) decarboxylated 1-(14C) glutamic acid liberating 14CO2. The reaction was pyridoxal phosphate-dependent and was inhibited by hydroxylamine, suggesting that it is a true amino acid decarboxylase. Loss of the activity at higher temperatures indicated the enzymatic nature of the reaction. Excess substrate or substrate analogs inhibited the decarboxylase whereas alpha-ketoglutarate and glutarate stimulated it. The activity was four times higher at pH 4.5 than at pH 6.8, suggesting that the enzyme is of microbial origin and not derived form the host cells. Armadillo spleen did not decarboxylate the amino acid. The Km value of the enzyme in the organisms was similar to that in Escherichia coli. The results reported here show that glutamate decarboxylase (EC 4.1.1.15) is an inherent metabolic activity of M. leprae, and might explain its unusual neural affinity. Glutamic acid is the most abundant amino acid occurring in the nerve tissue.

Carboxy-Lyases↗

Permeability of Mycobacterium leprae to dapsone: alteration by purification procedures.

Permeability of Mycobacterium leprae to dapsone in vitro was determined by the ability of the drug to inhibit o-diphenoloxidase of the bacilli. Dapsone showed little effect on the enzyme activity of the intact organisms. When the M. leprae preparations were washed with trypsin, NaOH, or acetone and ether, DDS penetrated the bacillus to inhibit its o-diphenoloxidase. The method might be useful in studying the utilization of added metabolites by purified M. leprae suspensions.

Animals↗

Osteosarcoma of the testis.

We studied a unique case of osteosarcoma of the testis. The tumor either originated from indifferent mesenchymal cells, or it represents a one-sided monomorphic development of a teratoma.

Humans↗

A possible method for improving the efficacy of dapsone.

The antileprosy drug dapsone is unable to penetrate intact Mycobacterium leprae in vitro, as determined by its effect on o-diphenoloxidase in the bacilli. When combined with the peptide polylysine, the sulfone drug passes through the bacterial cell membranes, and penetrates the enzyme protein, resulting in a 100% inhibition of its activity.

Catechol Oxidase↗