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Biomedical subjects

B S Sharma

Publications and source records attributed to B S Sharma.

At least 73 records · Page 4Linked to original sources
PubMed1990

Low molecular weight human T-cell response immunopotentiator: alpha-2'-deoxy-3-deazaguanosine.

We have examined the immunological activity of a unique alpha-nucleoside analog of 2'-deoxyguanosine in which the pyrimidine ring nitrogen in the 3 position is replaced by CH [6-amino-1, 5-dihydro-1-(2-deoxy-alpha-D-erythro-pentofuranosyl)imidazo[4,4-c] pyridin-4-one, alpha-d3DGuo, 1] and its structural analogs. The alpha-d3DGuo is not mitogenic to human PBL. It displayed consistently, however, a potent immunoenhancing activity on PHA-induced human lymphocyte proliferation at concentrations ranging from 0.0125 mM to 0.4 mM in a dose dependent manner. These findings thus suggest that mitogenicity is not a pre-requisite for the immunoenhancing effect. The maximal potentiating effect of alpha-d3DGuo is usually exerted at the bottom range of the dose response to PHA. The magnitude of increase is about the same as that mediated by rIL-2. Similarly, Con A mediated lymphocyte proliferation is markedly enhanced by alpha-d3DGuo. When added during allogeneic MLR, alpha-d3DGuo also augmented the proliferation of alloreactive T-cells and the magnitude of response was similar to that induced by rIL-2. The alpha-d3DGuo induced increase in allogeneic response was dependent on concentrations of both alpha-3dDGuo and alloantigens as noted with T-mitogen induced proliferative responses. The cytotoxic activity of lymphocytes induced in allogeneic mixed cultures was also augmented by alpha-d3DGuo. It showed, however, no potentiating effect on B-lymphocytes proliferation stimulated either with SAC or PWM. The alpha-d3DGuo is also able to restore, at least partially, the depressed proliferative responses of T-cells to both PHA and Con A.(ABSTRACT TRUNCATED AT 250 WORDS)

Adjuvants, Immunologic↗
PubMed1990

Actinomycotic brain abscess.

A histologically confirmed actinomycotic brain abscess, in a previously healthy female, is reported. CT scan findings of a thick walled multiloculated ring enhancement with smooth inner margin and irregular nodular enhancement of outer margin, along with contiguous patchy enhancing lesion with circular low attenuation areas were suggestive of a chronic granulomatous abscess. Surgical excision and prolonged antibiotic therapy produced a good resolution.

Actinomycosis↗
PubMed1990

Thiazolo[4,5-d]pyrimidine nucleosides. The synthesis of certain 3-beta-D-ribofuranosylthiazolo[4,5-d]pyrimidines as potential immunotherapeutic agents.

Novel analogues of the naturally occurring purine nucleosides were synthesized in the thiazolo[4,5-d]pyrimidine ring system to determine the immunomodulatory effects of insertion of a sulfur atom in place of nitrogen at position 7 of the purine ring. In particular, 5-amino-3-beta-D-ribofuranosylthiazolo[4,5-d]pyrimidine-2,7(3H,6H) -dione (7, guanosine analogue), 3-beta-D-ribofuranosylthiazolo[4,5-d]pyrimidine-2,5,7(3H,4H,6H) trione (8, xanthosine analogue), 3-beta-D-ribofuranosylthiazolo[4,5-d]pyrimidine-2,7(3H,6H)-dione (10, inosine analogue), and 7-amino-3-beta-D-ribofuranosylthiazolo[4,5-d]pyrimidin-2(3H)-one (32, adenosine analogue) were prepared, as well as the 8-mercaptoguanosine (14) and 6-mercaptoguanosine (17) analogues. Single-crystal X-ray studies confirmed the structural assignment of 17 and 32 as having the beta-configuration with the site of glycosylation at N3. The nucleosides were evaluated for their ability to potentiate various murine immune functions in direct comparison to the known active agents 8-bromoguanosine (1), 8-mercaptoguanosine (2), and 7-methyl-8-oxoguanosine (3). Two of the guanosine analogues, 7 and 14, were found to exhibit significant immunoactivity relative to the positive control compounds (1-3), while the adenosine, inosine, xanthosine, and 6-mercaptoguanosine analogues were devoid of activity. Compound 7 exhibited greater immunoactivity than any of the other guanosine analogues and derivatives in all test systems. Specifically, 7 was shown to be about twice as potent as 3 in the murine spleen cell mitogenicity assay. In addition, treatment with 7 produced about a 4-fold increase in natural killer cell cytotoxicity, while treatment with 3 afforded a 3-fold increase over controls. Finally, 7 provided excellent protection (92% survivors compared to 0% for placebo controls) against Semliki Forest virus in mice. Induction of interferon may account for the major mode of action of these guanosine analogues.

Adenosine↗
PubMed1990

Guanosine analogues. Synthesis of nucleosides of certain 3-substituted 6-aminopyrazolo[3,4-d]pyrimidin-4(5H)-ones as potential immunotherapeutic agents.

Several guanosine analogues were synthesized in the pyrazolo[3,4-d]pyrimidine ring system with various substituents at the 3-position. The new analogues prepared here include the CH3 (2-amino-3-methyl-1-beta-D-ribofuranosylpyrazolo[3,4-d]pyrimidin-4 (5H)-one, 13a), the phenyl (2-amino-3-phenyl-1-beta-D-ribofuranosylpyrazolo[3,4-d]pyrimidin-4 (5H)-one, 13b), and the NH2 (3,6-diamino-1-beta-D-ribofuranosylpyrazolo[3,4-d]pyrimidin-4(5H)- one, 17) substituted derivatives. These new agents, as well as several other 3-substituted derivatives including H, Br, OCH3, COOH, and oxo, were evaluated for their ability to potentiate certain murine immune functions relative to the known active agent 5-amino-3-beta-D-ribofuranosylthiazolo[4,5-d]pyrimidine-2,7(3H,6H) -dione (4, 7-thia-8-oxoguanosine). The biological evaluation included the (1) ex vivo determination of increased natural killer cell function and (2) in vivo antiviral protection against a lethal challenge of Semliki Forest virus. The 3-unsubstituted (5a) and the 3-bromo (5c) derivatives were found to be the most active immunopotentiators in this series.

Adjuvants, Immunologic↗
PubMed1990

Meningeal melanocytoma: report of two cases.

Two cases meningeal melanocytoma, one each at cranial and spinal location, are described. Neurological deficits in both cases improved following surgery. Pathological features of this rare tumour are discussed.

Adult↗
PubMed1990

Damage to the anterior visual pathway and brain parenchyma following external pituitary irradiation.

Three cases of damage to the optic nerves and chiasma following pituitary irradiation with Co60 teletherapy are described. All of them presented with progressive visual impairment months following irradiation and simulated recurrence of the tumour. CT scan was also not helpful in differentiating radionecrosis from tumour recurrence. On exploration the optic nerves and chiasma appeared discoloured and scarred. One case, who also had diffuse radionecrosis of brain parenchyma, died. No satisfactory therapy is currently available for this grave complication but proper safeguards can prevent it.

Adult↗
PubMed1989

Gliosarcoma with cartilage formation.

A case of gliosarcoma with cartilaginous component is described. Immunohistochemical and electron microscopic studies confirmed the presence of glial and fibroblastic elements. A major part of the sarcomatous tissue was undifferentiated and not labeled by any of the markers used including those for endothelial cells. The cartilage cells also were not labeled either by antiglial fibrillary acidic protein or any other marker. The occurrence and histogenesis of cartilage in gliomas and gliosarcomas have been reviewed.

Brain Neoplasms↗
PubMed1989

Nucleoside peptides. 10. Synthesis and T-cell immunostimulatory properties of certain peptide derivatives of 6-azacadeguomycin.

Several amino acid and peptide conjugates of 6-azacadeguomycin (6-amino-1-beta-D-ribofuranosyl-4,5-dihydro-4-oxopyrazolo[3,4-d]py rimidine- 3-carboxylic acid, 2) have been prepared in good yields, via a two-step procedure involving 1-hydroxybenzotriazole and 1-ethyl-3-[3-(dimethylamino)propyl]carbodiimide hydrochloride mediated coupling of 2 with an appropriately protected amino acid or peptide, followed by ammonolysis. Thus, condensation of 2 with L-phenylalanine methyl ester, glycine ethyl ester, and L-glutamic acid diethyl ester gave the corresponding protected linear nucleoside peptides (3, 5 and 7, respectively). Subsequent ammonolysis of 3, 5 and 7 furnished L-phenylalanine amide (4), glycine amide (6) and L-glutamic acid diamide (8) conjugates of 6-azacadeguomycin, respectively. Saponification of 7 gave the corresponding L-glutamic acid derivative 9. A similar coupling of 2 with L-phenylalaninyl-N epsilon-nitro-L-arginine methyl ester trifluoroacetate and subsequent ammonolysis (after catalytic hydrogenation) gave L-phenylalaninyl-L-arginine amide conjugate (12) of 6-azacadeguomycin. Compounds 2, 4, 6, 8, 9, and 12 were evaluated for their ability to potentiate T-cell responses to plant mitogens, in comparison with cadeguomycin (1). Compounds 4, 6, and 9 exhibited an increase in the T-cell proliferation in a dose-dependent manner.

Anti-Bacterial Agents↗
PubMed1989

Malignant schwannoma of brachial plexus presenting as spinal cord compression.

A 40-year-old male presented clinically with features of C6 radiculomyelopathy. An intradural extramedullary malignant schwannoma was removed at laminectomy. Foraminal extension of the tumour could not be removed in spite of foraminotomy, and no root attachment was found. Frequent intraspinal recurrences were treated with local resection. Delayed appearance of a supraclavicular mass, CT scan and exploration of supraclavicular fossa disclosed its origin from the upper trunk of brachial plexus.

Adult↗
PubMed1989

Broad-spectrum in vivo antiviral activity of 7-thia-8-oxoguanosine, a novel immunopotentiating agent.

A novel immunopotentiating agent, 5-amino-3-beta-D-ribofuranosylthiazolo [4,5-d]pyrimidine-2,7(3H,6H)-dione (7-thia-8-oxoguanosine), lacks virus-inhibitory properties in vitro but induces interferon and potentiates immune functions, such as natural killer cell activity. It was evaluated in rodent models to determine the spectrum of antiviral activity and effective treatment regimens. At 50 to 200 mg/kg given as single or divided intraperitoneal (i.p.) doses 1 day before virus inoculation, significant protection was afforded to mice infected i.p. with Semliki Forest, San Angelo, banzi, and encephalomyocarditis viruses. Similarly, suckling rats were protected from an intranasal challenge with rat coronavirus. Against San Angelo virus, treatments could be delayed to 1 day post-virus inoculation and still show a beneficial effect. The compound was moderately effective in mice infected i.p. with herpes simplex virus type 2 or intranasally with vesicular stomatitis virus. No activity was seen against influenza B virus in mice when the analog was administered one time pre-virus inoculation or in multiple doses given before and after the virus inoculation. Nor was there a prophylactic effect against herpetic skin lesions on mice. This immune modulator may have promise for the treatment of a variety of virus infections.

Adjuvants, Immunologic↗
PubMed1989

Thoracic disc herniation in acromegaly.

Herniation of a thoracic disc in an acromegalic giant is reported. Degenerative changes in the spine in association with dorsal kyphosis, and the additional strain, resulted in the disc prolapse.

Acromegaly↗
PubMed1989

Tension pneumocephalus following evacuation of chronic subdural haematoma.

Five cases of a rare complication of tension pneumocephalus following evacuation of chronic subdural haematoma are described. This occurred in 8% of all cases of chronic subdural haematoma treated following installation of a CT scanner. The chronically compressed brain contributes to the ingress of this intracranial air. The increase in the brain bulk and gradual re-expansion of the brain, in the early postoperative period, competes with the trapped subdural air resulting in a rise in intracranial pressure leading to neurological deterioration. Twist drill craniostomy and aspiration, using a brain cannula with a three-way connector, has produced excellent results.

Child↗
PubMed1989

Medulloblastoma in adults--clinical observations and results of treatment.

Ten cases of medulloblastomas, in patients above the age of 15 years, were treated during a 11 year period. These constituted 18 percent of all medulloblastomas and 1.2 percent of all primary brain tumours in adults during the same period. The majority of patients (80%) were between 16 and 25 years of age, and 80 percent were male. Half the patients presented within three months of the onset of symptoms. The usual clinical presentation was with features of raised intracranial pressure and cerebellar involvement. A lateral location of the tumour and its desmoplastic variant were common. Three patients survived more than five years. The desmoplastic variant and a gross total resection of the tumour favourably affected the prognosis. Posterior fossa recurrence was the chief cause of therapeutic failures. All the recurrences developed within three years of the initial diagnosis, and were fatal within six months of their detection.

Adolescent↗