Immunohistochemical detection of metallothionein expression and its correlation with ras activation in melanoma.
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Gene Expression Regulation, Neoplastic↗
Biomedical subjects
V K Shukla
Publications and source records attributed to V K Shukla.
Lipid peroxidation product in bile from patients with carcinoma of the gallbladder: a preliminary study.
Samples of gall bladder bile from patients with and without carcinoma of the gallbladder were examined for lipid peroxidation (free radical oxidation) products. 4-hydroxynonenal (HNE) was found in higher concentration in the bile of patients with carcinoma of the gall bladder. There was also a highly significant difference in the concentration of HNE among carcinoma of the gall bladder, cholelithiasis and control group of patients with miscellaneous abdominal disorders. This is the first study of lipid peroxidation in carcinoma of the gall bladder.
Aldehydes↗
Non-opioid effects of dynorphins: possible role of the NMDA receptor.
Dynorphin A (dynA) and related opioid peptides produce moderate analgesic effects with restricted types of pain stimuli that are often accompanied by a large variety of naloxone-insensitive biochemical and behavioural effects. In binding assays in vitro, dynA possesses a high affinity for mu-, delta- and kappa- opioid receptors with some selectivity for kappa sites, but it also binds to specific non-opioid sites. The involvement of the NMDA receptor has been suggested to explain some of the non-opioid effects of dynA and related peptides. In this article, Vijay Shukla and Simon Lemaire review the experimental evidence that suggests a role for the NMDA receptor in some of the pharmacological effects of dynA and related peptides.
Amino Acid Sequence↗
Serum trace elements and Cu/Zn ratio in malignant lymphomas in children.
Serum copper and zinc levels, and Cu/Zn ratio were measured in 40 children with Hodgkin's (n = 18) and non-Hodgkin's (n = 22) lymphomas, and 30 controls using Atomic Absorption Spectrophotometry. The mean serum copper levels were higher in lymphoma patients than in controls (199.8 micrograms/dl v. 95.8 micrograms/dl) P < 0.001). The increase in serum copper level correlated with the stage of disease being maximum in Stage IV (219.4 micrograms/dl v. 143.2 micrograms/dl) (P < 0.01). On the other hand, there was a decrease in the serum zinc levels in lymphoma patients as compared to controls (86.1 micrograms/dl v. 117.4 micrograms/dl) (P < 0.001), but this was significant only in patients with advanced disease. The Cu/Zn ratio was therefore markedly increased in these patients (2.46 v. 0.83) (P < 0.001). Following successful treatment the abnormal serum copper and zinc levels returned towards normal. The exact mechanisms responsible for these alterations are yet to be elucidated. We conclude that serum copper and zinc levels and Cu/Zn ratio are easily measurable biochemical indices that can be used as predictors of successful treatment in pediatric patients with lymphomas.
Adolescent↗
Perforated typhoid enteritis in children.
A prospective study of 65 patients with perforated typhoid enteritis managed operatively over a 3 year period at a university hospital is presented. There were 45 males and 20 females with ages ranging from 5 to 15 years. Presenting symptoms were fever, abdominal pain, vomiting and either diarrhoea or constipation. All the patients were subjected to surgery and 56 (86%) underwent two-layer bowel closure after freshening of ulcer margins. The overall mortality rate in this study was 20% and was adversely influenced by the increasing duration of perforation, presence of shock and faecal peritonitis. Early surgery after prompt and adequate resuscitation is life saving. However, prevention of typhoid fever by providing safe drinking water and better sanitary conditions appears to offer the best chance of decreasing the high rates of mortality and morbidity of this deadly disease.
Adolescent↗
Isolation and characterization of histogranin, a natural peptide with NMDA receptor antagonist activity.
Histogranin, was co-purified with bombesin-like immunoreactive peptides from bovine adrenal medulla. Its structure, H-Met-Asn-Tyr-Ala-Leu-Lys-Gly-Gln-Gly-Arg-Thr-Leu-Tyr-Gly-Phe-COOH, was determined by gas-phase Edman degradation. It was in accordance with its amino acid composition and corresponded to a 15 amino acid fragment (fragment 86-100) of histone H4 with substitutions in positions 1 (Val), 2 (Val) and 7 (Arg). The peptide was synthesized by the solid-phase procedure and the synthetic product was identical to the natural peptide as determined by its retention time on three analytical high-performance liquid chromatography systems. An antibody was raised against synthetic [Ser1]histogranin and used to monitor the presence of histogranin in various rat tissues and subcellular fractions of bovine adrenal medulla. In rats, immunoreactive histogranin was mainly concentrated in the pituitary (5065 pmol/g) and the adrenal glands (268 pmol/g), but it was also present in other tissues including the brain (1.6 pmol/g) and blood plasma (24 fmol/ml). A neuropeptide function for the adrenal peptide was suggested by its relative high concentration in chromaffin granules (42 fmol/mg protein as compared with 1 fmol/mg protein in cytosol) and its release from perfused bovine adrenal glands. In rat brain membrane preparations, synthetic histogranin displaced the binding of [3H]CGP 39653, a specific ligand of N-methyl-D-aspartate (NMDA) receptor. The displacement curve was biphasic with IC50 of 0.6 and 3955 nM, representing 33% and 67% of the binding sites, respectively. Intracerebroventricular (i.c.v.) injection of the peptide (5-100 nmol) in mice produced a dose-dependent protection against NMDA (0.5-1.0 nmol) -induced convulsions but not against (R,S)-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA, 0.25-2.0 nmol), kainate (0.25-0.75 nmol) and bicuculline (1-10 nmol)-induced convulsions. These results suggest that histogranin may be an endogenous modulator of NMDA receptor functions.
2-Amino-5-phosphonovalerate↗
Norbinaltorphimine protection against N-methyl-D-aspartic acid-induced convulsions and mortality.
The kappa-selective opioid antagonist, norbinaltorphimine (Nor-BNI), was tested against convulsions and mortality induced by the excitatory amino acids, N-methyl-D-aspartic acid (NMDA), (R,S)-alpha-amino-3- hydroxy-5-methyl-4-isoxazole propionate (AMPA) and kainic acid and the gamma-aminobutyric acid antagonist, bicuculline. Nor-BNI (10-40 nmol; intracerebroventricularly, i.c.v.) protected against NMDA (0.5-2.0 nmol i.c.v.)-induced convulsions and NMDA (2 nmol i.c.v.) and AMPA (2 nmol i.c.v.)-induced mortality. The opioid antagonist, naloxone (10 nmol i.c.v.), had no protecting activity. In vitro, Nor-BNI competed with the binding of the specific NMDA receptor ligand, [3H]D,L-(E)-2-amino-4-propyl- 5-phosphono-3-pentenoic acid ([3H]CGP 39653, 10 nM; IC50 of 1.63 +/- 0.20 microM) to mouse brain membrane preparations. The results indicate that the protecting activities of Nor-BNI are mediated by NMDA receptor-related mechanisms.
2-Amino-5-phosphonovalerate↗
Genetic and immunological analyses of the cyanobacterium Synechocystis sp. PCC 6803 show that the protein encoded by the psbJ gene regulates the number of photosystem II centers in thylakoid membranes.
The psbJ gene is a member of the psbEFLJ gene cluster in the cyanobacterium Synechocystis sp. PCC 6803 as well as in the chloroplasts of green plants. The putative product of the psbJ gene is a 4-kDa protein with one membrane-spanning domain. We have raised rabbit antibodies against a T7 gene 10-psbJ fusion protein, overexpressed in Escherichia coli. These antibodies recognized a polypeptide of expected size in the thylakoid membrane from wild type Synechocystis cells. We have also created a targeted mutant of Synechocystis 6803 in which the fourth codon of the psbJ open reading frame was modified to a translational stop codon. Thylakoid membranes from these mutant cells lacked the protein recognized by the antibodies. In the mutant cells, the partial electron transfer reaction mediated by the photosystem I complex was unaffected, whereas the rate of the photosystem II (PSII)-mediated reaction was 46% of that in wild type cells. Herbicide binding assays indicated that the PSII to chlorophyll ratio in the mutant cells was 49% of that in wild type cells. These results indicate that while the PsbJ protein is not essential for the photochemical activity it controls the amount of functionally assembled PSII complex in the thylakoid membrane.
Amino Acid Sequence↗
Serum and tissue trace elements in colorectal cancer.
Serum copper, zinc, and Cu/Zn ratio were measured using atomic absorption spectrophotometry in 30 patients with colorectal cancer and compared with 30 healthy control subjects. In the patients with colorectal cancer, the tissue copper and zinc levels were also measured in paired histologically normal and malignant colorectal tissue samples obtained at surgery. The mean serum copper levels were higher in patients with colorectal cancer (165.99 vs. 98.84 micrograms/dl) (P < 0.001). The mean serum zinc levels were lowered only in advanced (Dukes stages C and D) colorectal cancer compared to controls (89.94 vs. 115.08 mu/dl) (P < 0.001). However, the Cu/Zn ratio progressively increased with the advancing stage of malignancy (1.86 vs. 0.86) (P < 0.001). The cancerous colorectal tissue showed a higher concentration of both copper (2.78 vs. 1.79 micrograms/g) (P < 0.001) and zinc (27.16 vs. 18.98 micrograms/g) (P < 0.01) compared to non-cancerous colorectal tissue. The exact mechanism responsible for the alterations in trace element levels in patients with colorectal cancer is largely unclear and requires further evaluation. However, the serum copper level and the Cu/Zn ratio are of value in estimating the extent of the carcinoma as well as in determining the prognosis of these patients.
Adult↗
Biliary bile acids in cholelithiasis and carcinoma of the gall bladder.
The role of biliary deoxycholate as an endogenous carcinogen and the possible association between cholelithiasis and the subsequent development of carcinoma of the gall bladder is unclear. This paper describes biliary bile acid analysis performed on three groups of patients, 10 with cholelithiasis, 10 with carcinoma of the gall bladder and 10 control patients. This is the first report of bile acid changes in carcinoma of the gall bladder. In these 30 patients the total bile acids concentration was highly variable (11.44-53.68 mg/ml). The mean ratio of primary to secondary bile acids was 3.5:1. This ratio was, however, significantly higher in cholelithiasis than in the control group (5.34:1; P < 0.001); patients with carcinoma of the gall bladder had significantly higher secondary bile acids (1:1; P < 0.001). This is due to a marked increase in the secondary bile acids and indicates that raised biliary deoxycholate concentrations are present in patients with carcinoma of the gall bladder and therefore may well be a factor in carcinogenesis.
Bile Acids and Salts↗
Uterocutaneous fistula.
Fistulous communications of the uterus are relatively unknown. We report in this paper the first case to our knowledge of uterocutaneous fistula which developed following a septic abortion induced by introduction of Laminaria tent into the uterus.
Abortion, Septic↗
Gross rearrangements and deletions of the retinoblastoma gene are rare in malignant melanoma.
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Gene Deletion↗
Inoculation of a cultured autologous epidermal suspension containing melanocytes in vitiligo.
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Adolescent↗
Selective involvement of kappa opioid and phencyclidine receptors in the analgesic and motor effects of dynorphin-A-(1-13)-Tyr-Leu-Phe-Asn-Gly-Pro.
Dynorphin A-(1-13)-Tyr-Leu-Phe-Asn-Gly-Pro (Dyn Ia; 1-8 nmol) injected intracerebroventricularly in the mouse produces two independent behavioral effects: (1) a norbinaltorphimine (kappa opioid antagonist)-reversible analgesia in the acetic acid-induced writhing test and (2) motor dysfunction characterized by wild running, pop-corn jumping, hindlimb jerking and barrel rolling and antagonized by the irreversible phencyclidine (PCP) and sigma (sigma) receptor antagonist, metaphit and the non-competitive N-methyl-D-aspartate (NMDA) receptor antagonists, dextromethorphan and ketamine. The specific involvement of the PCP receptor in the motor effects of Dyn Ia is supported by the direct competitive interaction of the peptide with the binding of [3H]MK-801 (Ki: 0.63 microM) and [3H]TCP (Ki: 4.6 microM) to mouse brain membrane preparations.
Amino Acid Sequence↗
The D1 protein of the photosystem II reaction-centre complex accumulates in the absence of D2: analysis of a mutant of the cyanobacterium Synechocystis sp. PCC 6803 lacking cytochrome b559.
The reaction center core of photosystem II, a multiprotein membrane bound complex, is composed of a heterodimer of two proteins, D1 and D2. A random mutagenesis technique was used to isolate a photosystem II deficient mutant, CP6t16, of the unicellular cyanobacterium, Synechocystis sp. PCC 6803. Nucleotide sequence analysis showed that the primary lesion in CP6t16 is an ochre mutation introducing a translational stop codon in the psbE gene, encoding the alpha-subunit of cytochrome b559, an integral component of the PSII complex. Analysis of the protein composition of CP6t16 thylakoid membranes isolated in the presence of serine protease inhibitors revealed that, in the absence of cytochrome b559, the D2 protein is also absent. However, the D1 protein is stably incorporated in these membranes, suggesting that the synthesis and integration of D1 are independent of those of D2 and cytochrome b559.
Base Sequence↗
Central non-opioid physiological and pathophysiological effects of dynorphin A and related peptides.
Dynorphin A (Dyn A) and related opioid peptides derived from prodynorphin possess a high affinity for kappa opioid receptors, but they also bind to other opioid receptors (mu and delta) as well as to some non-opioid receptor sites. Although the physiological role of these peptides is not well established, recent experimental data pinpoint their particular involvement in physiological and pathophysiological conditions that relate to algesia, spinal cord injury and epilepsy. In this paper, we review data which support the concept that the non-opioid behavioral effects of Dyn A and related endogenous peptides which are observed under these conditions are physiologically and pathophysiologically relevant.
Brain↗
Role of rapid imprint cytology in the diagnosis of skin cancer and assessment of adequacy of excision.
Imprint cytotechnique was employed in 20 cases of maligant skin tumours (11 squamous cell carcinoma, 4 basal cell carcinoma and 5 malignant melanoma) to evaluate the reliability of the technique by comparing the results with histologic diagnosis. In ten cases margins of the excised tumours were also subjected to imprint and histopathologic studies to assess the clearance of malignancy. All the tumours were correctly diagnosed in imprint smears. Similarly 100% cytohistopathologic correlation was also obtained in the assessment of excisional margins of the tumours. The technique of imprint cytology may be employed for quick diagnosis of skin cancers and in assessment of clearance of surgical field during surgery.
Basal Cell Carcinoma↗
How common are benign subungual naevi?
The differentiation of subungual haematoma from benign and malignant nevoid lesions is a common clinical problem. To determine the incidence of benign subungual naevi in the general population, the digits of the hands and feet of 1000 white patients were examined. These were consecutive patients presenting to hospital for problems unrelated to the finger or toe-nail. Eight patients were found to have pigmented subungual lesions. All proved to be haematoma, although there was no history of injury. Benign subungual naevi are rare in caucasians, so subungual nevoid lesions should be regarded as malignant until proved otherwise.
Adolescent↗