Biomedical subjects

G Ramakrishna

Publications and source records attributed to G Ramakrishna.

24 records · Page 2Linked to original sources

PubMed2000

Poststreptococcal reactive arthritis in adults: a case series.

OBJECTIVE: To guide primary care physicians regarding the diagnosis and treatment of poststreptococcal reactive arthritis (PSReA) in adults. PATIENTS AND METHODS: We retrospectively reviewed an indexed database of all patients evaluated or hospitalized between 1976 and 1998 at Mayo Clinic Rochester and identified 35 patients with the diagnosis of reactive streptococcal arthritis, arthralgia, or arthritides. Twenty-nine patients with the diagnosis of acute rheumatic fever (ARF), septic streptococcal arthritis, or nonspecific reactive arthritis were excluded. RESULTS: PSReA was confirmed in 6 adults (3 women, 3 men; age range, 25-66 years). All patients were symptomatic with polyarthritis and oligoarthritis disproportionate to the objective findings on physical examination. Although all patients had negative throat cultures at the onset of arthritis, increased titers of anti-DNase B and antistreptolysin O confirmed recent streptococcal infection. Antecedent events included pharyngitis in 3 patients (who had received a minimum of a 10-day course of penicillin) and toxic shock syndrome in 1 patient. The latency of onset of arthritis ranged from 4 days to 6 weeks. The arthritic symptoms had a protracted course beyond the typical maximum of 3 weeks described for ARF. Treatment with aspirin did not provide symptomatic relief in any of the patients, whereas the response to therapy with nonsteroidal anti-inflammatory drugs (NSAIDs) was at least partial in all cases. Symptomatic relief occurred in 1 patient who received indomethacin and in 1 patient treated with prednisone. Penicillin prophylaxis was recommended in 1 patient. CONCLUSION: PSReA should be included in the differential diagnosis of all adult patients presenting with arthritis. Treatment strategies include aspirin, other NSAIDs, and corticosteroids. In adult patients with PSReA, there is no evidence to support the use of penicillin prophylaxis at this time.

Adult↗

PubMed2000

Churg-Strauss syndrome complicated by eosinophilic endomyocarditis.

A 34-year-old woman with asthma had increasing dyspnea on exertion for 9 months and new-onset mononeuritis multiplex. An examination demonstrated sinus tachycardia, elevated jugular venous pressure, and a tender nonpulsatile liver. The leukocyte count was 15.8 x 10(9)/L, with 23% eosinophils. Echocardiography revealed a laminated thrombus obliterating much of the right ventricular cavity, with encasement of the tricuspid valve. Ultrafast computed tomography showed no evidence of pulmonary emboli. Biopsy specimens of skin nodules revealed extravascular palisading granulomas. The thrombus was refractory to corticosteroids, and right ventricular thrombectomy was performed. To our knowledge, this is the third reported case of Churg-Strauss syndrome with thrombotic complications from coexistent eosinophilic endomyocarditis. In an asthmatic patient with chronic dyspnea, eosinophilic tissue infiltration, and neuropathy, Churg-Strauss syndrome should be considered; evaluation for cardiac involvement may be warranted.

Adult↗

PubMed1999

Reduced receptor expression for platelet-derived growth factor and epidermal growth factor in dividing mouse lung epithelial cells.

The roles of growth factors in mouse lung neoplasia were investigated by examining receptors for platelet-derived growth factor (PDGF) and epidermal growth factor (EGF) in epithelial cell lines. Whereas nontumorigenic lung cells expressed mRNA and protein for PDGF receptor (PDGFR)-alpha, PDGFR-beta, and EGF receptor (EGFR), five of six neoplastic lines did not. Because this exceptional tumorigenic cell line grows slowly, we hypothesized that receptor levels increased with cell stasis. To test this hypothesis, serum concentrations were manipulated, and log-phase and post-confluent cells were compared. Consistent with our hypothesis, PDGFR-alpha and EGFR contents, but not PDGFR-beta contents, increased at stasis. Ki-ras mutation initiates lung tumorigenesis in mice, but activation of Ki-ras did not affect receptor expression. This was determined both by transfecting nontumorigenic cells with activated Ki-ras and neoplastic cells with a Ki-ras antisense construct and by diminishing Ki-ras activation by using a farnesyltransferase inhibitor. Stasis-associated upregulation of growth-factor receptor expression suggests a function in lung cell differentiation that is abrogated during neoplastic growth.

Animals↗

PubMed1998

Selective mutation of K-ras by N-ethylnitrosourea shifts from codon 12 to codon 61 during fetal mouse lung maturation.

Fetal mouse lung before gestation day 17 shows unique sensitivity to causation of rapidly growing tumors by N-ethylnitrosourea (ENU). Since mouse lung tumors present a mutated K-ras oncogene, we hypothesized that this special susceptibility might reflect an unusual vulnerability of the K-ras gene. Of the lung tumors caused by ENU exposure of BALB/c mice on gestation day 14, 8/25 had a codon 12 mutation in K-ras, vs 4/25 in codon 61. Of 15 tumors after day 16 exposure, three had codon 12 and four codon 61 changes. Tumors from day 18 exposure had only codon 61 mutations (11/16), all A:T to G:C changes (CGA). By contrast, codon 12 (GGT) changes included G:C to T:A, to A:T, and to C:G. These results show significant (P<0.01) shift in the sensitivity of particular K-ras codons to ENU mutation, during fetal mouse lung maturation. In a test of a possible relationship to expression of K-ras, K-ras p21 was measured in lungs of fetal mice, and found to increase markedly on day 18 in comparison to days 14 and 16. Both alkylation of DNA and base damage due to reactive oxygen species are postulated as mechanisms for mutation by ENU, whose efficacies vary with state of fetal lung maturation and K-ras expression.

Adenocarcinoma, Papillary↗

PubMed1998

Levels and membrane localization of the c-K-ras p21 protein in lungs of mice of different genetic strains and effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and Aroclor 1254.

Mutational activation of the K-ras oncogene often occurs in human and mouse lung adenocarcinomas. Since K-ras p21 functions in trans-membrane signaling, we have investigated whether the amount of this protein in lung cell membranes is a variable that could influence lung tumorigenesis, either due to genetic differences or in response to tumor promoters. The six mouse strains assessed showed little difference in the total lung K-ras p21 after immunoprecipitation and immunoblotting. However, amount of ras p21 in the membrane fraction showed significant differences, with C57BL/6 and BALB/c having 3-5-fold more than NIH Swiss, AKR and DBA mice. Interestingly, a congenic AKR strain having the Ahr(b-1) Ah receptor allele from C57BL/6 mice (designated AKR.B6Ah) had high lung membrane K-ras p21 similar to that of C57BL/6. To test for possible changes related to lung tumor promotion, mice were treated with a promotional dose of TCDD (5 nmol/kg). After 48 h C57BL/6 lungs showed an increase in p21 in both total and membrane fractions. BALB/c, DBA and Swiss mice showed an increase only in membranes. There was no change in the AKR and AKR.B6Ah. Aroclor 1254 (250 mg/kg) caused an increase in membrane/cytosol ratio in Swiss mice. Thus the membrane:cytosol K-ras p21 ratio may be influenced by the Ahr phenotype, and TCDD and PCBs can induce p21 or increase its membrane level in certain strains, but these properties are not fully dependent on Ahr receptor type. In confirmation of the relevance of these findings for the tumor target cell type, the immortalized alveolar type 2 E10 cell line presented K-ras p21 in membrane, and this was increased 4-fold by treatment with 10 nM TCDD.

Adenocarcinoma↗

PubMedDate not supplied

Overexpression of Grb2 in inflammatory lesions and preneoplastic foci and tumors induced by N-nitrosodimethylamine in Helicobacter hepaticus-infected and -noninfected A/J mice.

Growth factors bind to membrane receptor tyrosine kinases, resulting in autophosphorylation and subsequent binding to proteins with SH2 domains, including growth factor receptor-bound protein 2 (Grb2). Grb2 bridges receptors to tyrosine kinase substrates such as SHC and SOS, which in turn facilitate the activation of downstream signaling pathways, including Ras and mitogen-activated protein kinase (MAPK). Overexpression of Grb2 has been demonstrated in several types of neoplasia but has not been investigated in liver tumorigenesis. Here we investigated Grb2 expression in liver lesions in N-nitrosodimethylamine (NDMA)-treated Helicobacter hepaticus-infected and -noninfected A/J mice at 1 year of age. Previously, we reported (6) that infection promotes the development of these NDMA-initiated tumors. In controls, Grb2 immunostaining was absent from normal hepatic tissues, whereas the inflammatory lesions in infected livers were positive for cytoplasmic Grb2 in both hepatocytes and infiltrating leukocytes. All preneoplastic foci (7 of 7), 15 of 27 adenomas, and 3 of 7 carcinomas were positive for Grb2 by immunostaining in both infected and noninfected NDMA-initiated livers. Involvement of Grb2 was confirmed by immunoblotting of similarly infected mice at 9 to 18 months of age, showing a 2.5- to 3.3-fold increase in Grb2 protein in infected livers (p < 0.05 compared with uninfected controls) as well as in preneoplastic foci, adenomas, and carcinomas. These livers also showed a 2.5- to 2.8-fold increase in total Ras protein. The results suggest that upregulation of Grb2 is an early event in liver carcinogenesis, whether caused by the bacterial infection or by NDMA. Concomitant upregulation of Ras p21 would ensure transmission of amplified signal from growth factors via Grb2.

Adaptor Proteins, Signal Transducing↗