PubMed HealthSearch

Biomedical subjects

G Ramaswamy

Publications and source records attributed to G Ramaswamy.

At least 19 recordsLinked to original sources

Cloning and characterization of a eukaryotic pantothenate kinase gene (panK) from Aspergillus nidulans.

Pantothenate kinase (PanK) is the key regulatory enzyme in the CoA biosynthetic pathway. The PanK gene from Escherichia coli (coaA) has been previously cloned and the enzyme biochemically characterized; highly related genes exist in other prokaryotes. We isolated a PanK cDNA clone from the eukaryotic fungus Aspergillus nidulans by functional complementation of a temperature-sensitive E. coli PanK mutant. The cDNA clone allowed the isolation of the genomic clone and the characterization of the A. nidulans gene designated panK. The panK gene is located on chromosome 3 (linkage group III), is interrupted by three small introns, and is expressed constitutively. The amino acid sequence of A. nidulans PanK (aPanK) predicted a subunit size of 46.9 kDa and bore little resemblance to its bacterial counterpart, whereas a highly related protein was detected in the genome of Saccharomyces cerevisiae. In contrast to E. coli PanK (bPanK), which is regulated by CoA and to a lesser extent by its thioesters, aPanK activity was selectively and potently inhibited by acetyl-CoA. Acetyl-CoA inhibition of aPanK was competitive with respect to ATP. Thus, the eukaryotic PanK has a distinct primary structure and unique regulatory properties that clearly distinguish it from its prokaryotic counterpart.

Amino Acid Sequence

Circulating levels in serum of total sialic acid, lipid-associated sialic acid, and fucose in precancerous lesion and cancer of the oral cavity.

Total sialic acid (TSA), lipid-associated sialic acid (LASA), and fucose were estimated in sera of 35 patients with precancerous lesion of the oral cavity, 68 patients with cancer of the oral cavity, and 25 age- and sex-matched non-chewers of both tobacco and betal nut and nonsmokers as controls. Significant elevation in the serum levels of TSA and LASA were observed in patients with the precancerous and cancer lesions when compared with the controls. Serum TSA levels were elevated significantly in patients with cancer when compared with those with precancerous lesions. Circulating TSA and LASA levels were found to reflect tumor burden and correlated well with stage of the disease. However, serum fucose levels did not show an increase corresponding to stage of the disease. The results suggests that combined evaluation of these markers may be useful in predicting early malignant change and also in assessing the spread and invasiveness of the disease in cancer of the oral cavity.

Biomarkers, Tumor

Serum vitamins' status in oral leucoplakias--a preliminary study.

Vitamins, such as A, beta carotene, C, E, B12 and folate, are the micronutrients with the strongest evidence of having a link to cancer prevention and control. Deficiency of these vitamins at the dietary, systemic or mucosal level will interact with tobacco use and increase the risk of oral precancerous lesions. The objective of this study was to (1) establish the baseline circulating levels of these vitamins in our normal population with and without tobacco use and (2) compare these levels with the values obtained in cases of oral leucoplakias. 50 normal controls with 25 each in chewers and non-chewers, matched for age and sex, were selected. 50 cases of oral leucoplakias (clinically detectable white patches) from the field constituted the study group. Simultaneous measurement of serum vitamin B12 and folate were carried out by radioassay. The other serum vitamins were estimated spectrophotometrically. Except for serum vitamin E, all the other serum vitamin levels were significantly decreased in oral leucoplakias compared to the controls. Cancer chemopreventive agents acting as inhibitors of both initiation and promotion, as analysed in our population, is promising for further intervention trials.

Ascorbic Acid

Serum carotene, vitamin A, and vitamin C levels in breast cancer and cancer of the uterine cervix.

Levels of carotene, vitamin A, and vitamin C measured in the serum of patients with cancer of the breast and uterine cervix were compared with levels in healthy controls and patients with benign diseases of the breast and cervix. Serum ascorbate levels were significantly lower in patients with benign diseases of the breast and cervix than in controls. In cancer patients, there was a significant trend of lower serum vitamin levels with increasing stage of the disease.

Ascorbic Acid

Poorly differentiated pediatric head and neck neuroblastoma: a diagnostic dilemma.

Primary pediatric head and neck neuroblastoma is rare, with metastatic disease being the more common mode of involvement in this anatomic region. Poorly differentiated neuroblastoma initially presenting in head and neck locations presents a diagnostic dilemma, especially when evidence of primary disease in typical abdominal, retroperitoneal and thoracic sites is lacking. This tumor cannot easily be distinguished from the other common pediatric small round cell malignancies that may originate in or metastasize to the head and neck. Recent years have seen great strides in the immunohistochemical as well as cytogenetic characterization of certain pediatric small round cell lesions. A never before reported solitary, poorly differentiated neuroblastoma of the right parotid gland in a 20-month-old female is presented in order to familiarize the otolaryngologist with the modern diagnostic armamentarium available for the accurate characterization, and thus appropriate workup and treatment of this disease.

Diagnosis, Differential

A new scale for assessing behavioral agitation in dementia.

The primary purpose of the present study was to develop a reliable and valid rating instrument for assessing treatment efficacy for behavioral problems in the cognitively impaired elderly. The Behavioral and Emotional Activities Manifested in Dementia (BEAM-D) Scale was developed for the operational assessment of troublesome and disruptive behaviors in dementia. Each behavioral category of the BEAM-D was clinically considered to be a significant deviation from normative behavior for the geriatric dementia patient. The reliability and validity of the BEAM-D was assessed in a group of 45 patients diagnosed with primary degenerative dementia. The mean interrater reliability of BEAM-D items was 0.90. Concurrent validity was established by comparison with currently used rating scales, the Brief Psychiatric Rating Scale (BPRS) and the Sandoz Clinical Assessment-Geriatric (SCAG). Stepwise regression analysis revealed that the items of the BEAM-D had a strong relationship with conceptually similar behavioral dimensions on the BPRS and SCAG.

Aged

Augmentation of the effect of doxorubicin with low-dose tumor necrosis factor in experimental liver metastasis.

The antitumor activity of recombinant human tumor necrosis factor was studied in vivo as a single agent and in combination with a conventional chemotherapeutic agent. Dosages of tumor necrosis factor of 100 micrograms, 50 micrograms, and 25 micrograms were injected intraportally in Sprague-Dawley rats containing hepatic implants of Walker carcinosarcoma. An effect on the tumor was seen but was associated with a significant acute mortality. Lower dosages of tumor necrosis factor, 10 micrograms, 5 micrograms, and 1 microgram, administered with 10 mg/kg of doxorubicin (Adriamycin) significantly enhanced the antitumor effect of doxorubicin without an acute mortality. This suggests that lower dosages of tumor necrosis factor with conventional chemotherapy may augment the latter's effect without any added toxicity.

Animals

Immunological abnormalities in autoimmune chronic active hepatitis.

Autoimmune chronic active hepatitis is often associated with clinical and laboratory features that resemble those observed in systemic lupus erythematosus (SLE). We describe a 24-year-old woman with autoimmune chronic active hepatitis who was studied for serologic markers of autoimmunity and for immune clearance in terms of in vivo Fc receptor function. A markedly depressed immune clearance and splenic uptake of radiolabelled and IgG coated autologous erythrocytes was observed. The magnitude of this defect equaled or exceeded the most severe defects seen in a group of patients with SLE. This phenomenon was associated with markedly depressed serum C4 levels, a variably positive Sm antibody, and normal circulating immune complex concentrations. In addition, many clinical extrahepatic manifestations meeting criteria for classifying SLE were present. These findings further support the concept of autoimmune chronic active hepatitis and SLE being part of spectrum of overlapping autoimmune diseases.

Adult

Enhancement of tumor blood flow and tumoricidal effect of doxorubicin by intraportal epinephrine in experimental liver metastasis.

Laser Doppler capillary perfusion monitoring was performed in 25 Sprague-Dawley rats with solitary intrahepatic implants of Walker carcinosarcomas. Doses of intraportal epinephrine from 1 to 10 micrograms produced an immediate rise in capillary blood flow, reaching peak levels by 16 s. The increased flow lasted an average of 57 s. Because epinephrine selectively increased tumor blood flow, studies were performed to determine if enhancement of the chemotherapeutic effect of doxorubicin could be achieved. Forty-two rats with seven-day hepatic implants were treated sequentially with intraportal epinephrine (10 micrograms) and doxorubicin hydrochloride (10 mg/kg) or doxorubicin alone. After only two courses of chemotherapy, a significant difference in necrosis and cell viability was obtained in those animals treated with epinephrine intraportally prior to doxorubicin infusion. Enhancement of the tumoricidal effect of chemotherapy can be achieved by manipulating the blood flow to developing tumors pharmacologically.

Animals

Epithelioid hemangioendothelioma of penis.

A case of epithelioid hemangioendothelioma of the penis in a sixty-year-old patient is reported. This is a rare vascular tumor of borderline malignant potential. Local excision of this tumor with a cuff of normal tissue and careful follow-up of the patient is the accepted procedure.

Diagnosis, Differential

Pseudogaucher cells in Mycobacterium avium intracellulare infections in acquired immune deficiency syndrome (AIDS).

This report describes a 28-year-old woman with the acquired immune deficiency syndrome (AIDS) with culture-proven disseminated Mycobacterium avium intracellulare infection. The histopathologic and cytologic features in this case were unique in that these organisms that stained positively with the Ziehl-Neelsen and periodic acid-Schiff (PAS) stains were numerous, present intracellularly within histiocytes, transforming them into pseudogaucher cells. Differential diagnostic criteria for pseudogaucher cells and abnormal macrophage handling of the intracellular organisms in AIDS are discussed.

Acquired Immunodeficiency Syndrome

Histochemical determination of copper, zinc, and iron in some benign and malignant tissues.

Histochemical tests for copper, iron, and zinc revealed their presence in the stratum germinativum of normal skin and skin from which an early melanoma and basal cell and squamous cell carcinomas originated. However, only copper was seen in invasive cells of basal and squamous cell carcinomas originating from skin. The normal oral mucous membrane was free of copper, iron, and zinc, but cells of invasive squamous carcinoma originating from the oral mucous membrane contained copper. The fluorescent brightening agent, applied as a counterstain, aided in the location of the specimen.

Basal Cell Carcinoma

A testicular tumor resembling the sex cord with annular tubules in a case of the androgen insensitivity syndrome.

Sex cord tumor with annular tubules (SCTAT) is a distinctive neoplasm with indifferent cells of sex cord derivation in a characteristic arrangement of ring-like tubules. Much attention has been drawn to its association with the Peutz-Jeghers syndrome (PJS) with reported occurrence of the tumor in the testis of a boy with PJS. The authors present two cases of the androgen insensitivity syndrome (AIS), one of the cases being distinctive in having a large multicystic tumor resembling the SCTAT in the immature gonad. Additionally, the focal areas of the tumor, the large Sertoli cells lining the tubules, resembled those of a large cell calcifying Sertoli cell tumor (LCCSCT) although no calcific areas were discernible. Although the occurrence of neoplasms like germinomas and tubular adenomas is well known in the AIS, SCTAT has hitherto not been reported in a gonad of the AIS. SCTAT has been placed under an "unclassified sex cord-stromal" category in the World Health Organization (WHO) Classification, yet, opinions are divided as to its origin from a granulosa or Sertoli cell, although an overlap in the histologic features of the two cell categories is to be anticipated in view of their homologous nature. In the case presented, the close resemblance of the tumor cells to the Sertoli cells of the uninvolved gonad would further support the concept of a Sertoli line of differentiation of the SCTAT.

Adult

Diffuse alveolar damage and interstitial fibrosis in acquired immunodeficiency syndrome patients without concurrent pulmonary infection.

Patients with acquired immunodeficiency syndrome (AIDS) characteristically present with repeated pulmonary infections. We present the pathologic findings in lung biopsy specimens from 12 patients with AIDS in whom the histologic spectrum ranged from mild diffuse alveolar damage to frank interstitial fibrosis. In all of these patients, there was no evidence of any concurrent infectious process in the lung. Diffuse alveolar damage is a pattern of response of the lung to many kinds of infectious processes and immunologic injury, both of which are potential possibilities in patients with AIDS. This study underscores the development of diffuse alveolar damage or interstitial fibrosis and their presentation as the sole histologic findings in lung biopsy specimens from patients with AIDS. We discuss the possibility that these changes may be long-term sequelae to repeated pulmonary infections with or without an immunologic defect.

Acquired Immunodeficiency Syndrome