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Biomedical subjects

A K Malik

Publications and source records attributed to A K Malik.

At least 19 recordsLinked to original sources

Genetic analysis of the herpes simplex virus type 1 UL9 gene: isolation of a LacZ insertion mutant and expression in eukaryotic cells.

HSV-1 host range mutants in complementation group 1-36 (hr27 and hr156) whose mutations map in the UL9 gene, encoding the origin binding protein, are unable to form plaques or synthesize viral DNA or late viral proteins when grown in nonpermissive Vero cells (Carmichael, E. P., Kosovsky, M. J., Weller, S. K., 1988, J. Virol. 62, 91-99). These defects are complemented efficiently by growth in the permissive cell line, S22, which contains the wild type version of several HSV genes including UL9. In this report the precise nature and location of the lesions in host range mutants hr27 and hr156 were determined by DNA sequencing; both mutants were found to contain identical single-base-pair substitutions at codons 309 and 311 in the UL9 open reading frame. This region lies within the putative helicase domain of the UL9 protein. The UL9 gene was disrupted by the insertion of an insertional mutagen ICP6::lacZ in which the Escherichia coli lacZ gene is expressed under control of the viral ICP6 promoter. Hr94, a viral mutant containing this insertion, does not form plaques or synthesize viral DNA when grown in Vero cells, although both defects are complemented efficiently on permissive cell lines. These results confirm that the UL9 gene product is essential for viral growth and DNA replication. Furthermore, since no detectable UL9 protein is synthesized in hr94-infected cells, this virus provides a useful genetic background for further structure-function analysis since no potentially interfering nonfunctional UL9 protein will be expressed. We have expressed the UL9 open reading frame under the control of the strong and inducible HSV-1 ICP6 promoter and have derived Vero cell lines containing variable copy numbers of the ICP6::UL9 construct. Cells whose copy number of this construct exceeded approximately 120 are unable to support efficient plaque formation by wild-type virus. Cell lines with low copy numbers of this construct are able to complement hr27, hr156, and hr94.

Amino Acid Sequence

Quantitation of immunoglobulin-containing cells in the jejunal lamina propria in tropical sprue.

Ten patients with tropical sprue (TS) and 10 with irritable bowel syndrome (IBS) as controls were studied to characterize the immunocytes in the jejunal mucosa. IgA cells numbered 516,155 +/- 48,715 cells/mm3 in TS and 729,308 +/- 146,011/mm3 in the IBS patients. IgG cell counts were 28,885 +/- 8,081/mm3 in TS and 10,615 +/- 4,100/mm3 in IBS; IgM counts were 170,729 +/- 25,015/mm3 in TS and 169,253 +/- 45,353/mm3 in IBS. A positive correlation was present between IgM-bearing plasma cells and corresponding serum immunoglobulins (r = +0.71; p less than 0.05). No correlation was evident between the different immunocytes (IgA, IgG, and IgM) and the duration of illness, serum albumin, and tests for absorption of fat, B-12, and D-xylose (p greater than 0.05). The gut immunocytes expressed in absolute numbers were higher in our controls and TS patients than reported in Western populations.

Adult

Optimal number of biopsy specimens in the diagnosis of carcinoma of the oesophagus.

The study evaluated 48 patients with carcinoma of the oesophagus to assess the optimal number of biopsy specimens required to obtain the highest yield. Eight specimens were obtained from each patient and two specimens were placed serially in each of four vials. The first vial provided a positive diagnosis in 95.8% of cases. The addition of two more specimens (second vial) increased the yield to 97.9% and the fifth and sixth specimens increased the positive yield to 100%. There was no statistically significant difference in the yield according to the site and the type of growth.

Adult

Periampullary carcinoma with special reference to their mucin characteristics--a pathologic study of 53 cases.

Histological features and mucin characteristics of 53 cases of periampullary carcinoma, a rare group of epithelial tumors is presented. The cases comprised of 17 resected specimens and 36 endoscopic biopsies. Jaundice was the commonest symptom. The mean tumor size was 2 cms diameter (1-6 cms). Forty cases were characterised as well differentiated adenocarcinoma, 5 as moderately differentiated adenocarcinoma, 5 as mucin secreting adenocarcinoma, 3 as papillary adenocarcinoma and 1 as undifferentiated carcinoma. Desmoplasia and insignificant mitosis were amongst the commonly encountered histological features. Forty four cases (83%) stained positive for mucin (PAS-AB) with a majority of them (66%) predominantly showing acidic mucin. The likely prognostic implication of this feature is discussed.

Adenocarcinoma

Immunoperoxidase localization of fibronectin in small bowel mucosa.

An indirect immunoperoxidase technique was employed to demonstrate fibronectin in cryostat sections of small bowel mucosa. Prior exposure of the sections to a solution of pepsin (4 mg/ml) was not essential to localize antigenicity of fibronectin immunohistologically.

Biopsy

Fatal pulmonary arterial hypertension complicating noncirrhotic portal fibrosis.

A 25-yr-old female with noncirrhotic portal fibrosis underwent a lienorenal shunt for variceal bleed. Ten years after shunt surgery, she presented with progressive breathlessness, and severe pulmonary arterial hypertension was detected, to which she subsequently succumbed. Autopsy revealed classical plexogenic pulmonary arteriopathy.

Adult

Niemann-Pick disease presenting as hepatic disorder.

A 2 year old female child with Niemann-Pick disease was referred as case of chronic liver disease; clinically, she had neurological involvement. Liver biopsy showed Niemann-Pick cells. Hepatic manifestations of Niemann-Pick disease as seen in nine cases reported from India are discussed.

Child, Preschool

Visceral larva migrans in an adult.

Visceral larva migrans is rare in adults. An adult male in whom the diagnosis was made by suggestive clinical features and muscle biopsy and who responded to thiabendazole is described.

Adult

Analysis of the interactions of functional domains of a nuclear origin of replication from Saccharomyces cerevisiae.

We have determined that ARS121 is an efficient origin of replication on chromosome X of Saccharomyces cerevisiae. This origin is comprised of at least three distinct functional domains. One of these domains is the ARS121 core sequence (approximately 35 bp-long), which is essential for origin activity. This essential core contains an 11 bp sequence resembling (2 bp mismatch) the ARS consensus. Another important domain is an enhancer of DNA replication, which binds the OBF1 protein. The third domain, ATR (A/T-rich, approximately 72 bp), is auxiliary and works in either orientation, but only when located 3' to the essential core. When fused to the ARS121 core both the enhancer and the ATR domain act synergistically to enhance the activity of the origin. Furthermore, when fused to the essential core sequences of heterologous ARSs, ARS1 and ARS307, the auxiliary domains also appeared to stimulate synergistically origin function. These results suggest that (i) in order to elicit maximal origin activity all three domains have to interact and (ii) activation of the essential core sequences at different origins of replication may share a common mechanism.

Base Sequence

Morphological and functional characterization of a hormonally induced AIMS/GRXII cell line.

The AIMS/GRXII cell line is a product of the line of research our laboratory is pursuing to understand the response of target cells to sustained hormonal stimulation, a situation simulating the one that brings about in vivo tumorigenesis. The cell line was derived from goat ovarian granulosa cells subjected to luteinizing hormone stress (high doses repeated). It was found to be contact-inhibited, nontumorigenic and secreted progesterone. The majority of cells at any given passage showed hypodiploidy. The cell line required hormonal support till passage 8 after which it was hormone-independent. Thus, the system offers a phase-wise development of the cell line which might be useful in cancer research, particularly to understand the mechanisms of cell transformation at the cellular and molecular level and possible hormone (onco)gene nexus in cell proliferation.

Animals

The AIMS/GRXVIII cell line: 'spontaneous' transformation of hormonally induced primary cells derived from goat ovarian granulosa.

AIMS/GRXVIII is one of the cell lines developed in our laboratory from goat ovarian granulosa cells by luteinizing hormone (LH) stress. Unlike other cell lines in the AIMS/GR series which were contact-inhibited and non-tumorigenic, this one was 'spontaneously' transformed during passage 14 with a doubling time of 20 h. The morphology changed from a spindle shape to epithelial-like. Cultures lost contact inhibition and presented extensive mitotic and chromosomal abnormalities. The cultures secreted progesterone even without LH support after passage 8. The cells developed small tumours of luteal morphology in hamster cheek pouches, though they failed to form colonies in soft agar gel. This is a functional cell line and should be useful in understanding various processes in cell biology like function, signal transduction and mechanisms of cell transformation.

Animals