Biomedical subjects
Publications and source records attributed to S Saha.
A four year old boy was referred from Scotland, with a seasonal pattern of depressive symptoms dating back to infancy and meeting criteria for Major Depressive Disorder with Seasonal Pattern by the age of three years. There was consistency in reports between informants and across contexts and significant improvement with light therapy.
Biochemical and immunocytochemical analyses have been used to provide new insights into age-related changes in the sensory and supporting cells of the guinea pig organ of Corti. Quantitative densitometry of immunoblots showed that, while levels of alpha-tubulin remained relatively constant in guinea pigs from 3 weeks to 18 months old, there were progressive shifts in some tubulin isoforms. Levels of tyrosinated tubulin increased with age, nontyrosinatable tubulin (delta2-tubulin) showed a compensatory decrease, but detyrosinated tubulin did not change; acetylated, polyglutamylated, and glycylated tubulin levels also decreased. Immunolabeled tissue sections showed that cell type-specific distribution of tubulin seen in young guinea pigs (tyrosinated in the microtubules of the sensory cells, and post-translationally modified isoforms in the supporting cells) did not change as animals aged. However, there were age-related decreases in labeling for alpha-tubulin and all post-translationally modified isoforms. Biochemical and immunocytochemical results both support an age-related decrease in the number and/or length of microtubules as well as an increase in the pool of soluble tyrosinated and detyrosinated tubulin. They further suggest that microtubules containing nontyrosinatable tubulin from older animals are the sites for further modification of tubulin by acetylation, polyglutamylation, and glycylation. Changes in tubulin isoform levels and stability of microtubules in the organ of Corti may alter its micromechanical properties; the resulting changes in conduction of sound-induced vibration would provide one mechanism for age-related hearing loss.
BACKGROUND: Sentinel lymph node (SLN) mapping for melanoma and breast cancer has greatly enhanced the identification of micrometastases in many patients, thereby upstaging a subset of these patients. The purpose of this study was to see if SLN mapping technique could be used to identify SLNs in colorectal cancer and to assess its impact on pathological staging and treatment. METHODS: At the time of surgery, 1 ml of Lymphazurin 1% was injected subserosally around the tumor without injecting into the lumen. The first to fourth blue nodes identified were considered the SLNs, which have the highest probability to contain metastases. A standard oncological resection of the bowel was then performed. Multilevel microsections of the SLNs, including a detailed pathological examination of the entire specimen, was performed. RESULTS: SLN was successfully identified in 85 (98.8%) of 86 patients. In 85 patients, there were 1,367 (16 per patient) lymph nodes examined, of which 140 (1.6 per patient) were identified as SLNs. In 53 (95%) of 56, of whom the SLNs were without metastases (negative), all other non-SLNs also were negative. In 29 (34% of 85) patients, SLNs were positive for metastases; in 14 of the 29 patients, other non-SLNs also were positive in addition to the SLNs. In the other 15 of the 29 patients (18% of 85 patients), SLNs were the only site of metastases, and all other non-SLNs were negative. In 7 patients (8.2% of 85 patients), micrometastases were identified only in 1 or 2 of the 10 sections of a single SLN. In five of seven patients, such micrometastases were detected by hematoxylin and eosin staining and immunohistochemistry; in the other two patients, it was detected only by immunohistochemistry. In patients with negative SLNs, the rate of occurrence of micrometastases in non-SLNs was 5 (0.4%) of 1,184 lymph nodes. CONCLUSIONS: SLN mapping can be performed easily in colorectal cancer patients, with an accuracy of more than 95%. The identification of submicroscopic lymph node metastases by this technique may have upstaged these patients (18%) from stage I/II to stage III disease, who may then benefit from further adjuvant chemotherapy.
Sentinel lymph node (SLN) mapping has been found to be highly effective in correctly predicting the nodal status for melanoma and for breast cancer. This study shows that SLN mapping also is highly successful in colorectal cancer, posing minimal cost and no complications. The procedure accurately determines the presence or absence of nodal micrometastasis in more than 96% of cases. This article reviews the in vivo and ex vivo techniques for SLN mapping in colorectal cancer, along with its limitations and pitfalls.
The phenomenon of restriction and modification (R-M) was first observed in the course of studies on bacteriophages in the early 1950s. It was only in the 1960s that work of Arber and colleagues provided a molecular explanation for the host specificity. DNA restriction and modification enzymes are responsible for the host-specific barriers to interstrain and interspecies transfer of genetic information that have been observed in a variety of bacterial cell types. R-M systems comprise an endonuclease and a methyltransferase activity. They serve to protect bacterial cells against bacteriophage infection, because incoming foreign DNA is specifically cleaved by the restriction enzyme if it contains the recognition sequence of the endonuclease. The DNA is protected from cleavage by a specific methylation within the recognition sequence, which is introduced by the methyltransferase. Classic R-M systems are now divided into three types on the basis of enzyme complexity, cofactor requirements, and position of DNA cleavage, although new systems are being discovered that do not fit readily into this classification. This review concentrates on multisubunit, multifunctional ATP-dependent restriction enzymes. A growing number of these enzymes are being subjected to biochemical and genetic studies that, when combined with ongoing structural analyses, promise to provide detailed models for mechanisms of DNA recognition and catalysis. It is now clear that DNA cleavage by these enzymes involves highly unusual modes of interaction between the enzymes and their substrates. These unique features of mechanism pose exciting questions and in addition have led to the suggestion that these enzymes may have biological functions beyond that of restriction and modification. The purpose of this review is to describe the exciting developments in our understanding of how the ATP-dependent restriction enzymes recognize specific DNA sequences and cleave or modify DNA.
The central nucleus of the amygdala is involved in the modulation of autonomic, somatic and endocrine functions, as well as behavioural responses to stressful stimuli. Anatomical and physiological studies have suggested that this nucleus sends projections to the nucleus of the solitary tract, the primary site of termination of vagal and glossopharyngeal afferent fibres in the brain stem. To determine the neurochemical nature of the amygdaloid input to the nucleus of the solitary tract, anterograde tracing with biotinylated dextran amine was combined with post-embedding immunogold labelling for GABA and glutamate immunoreactivities and with pre-embedding labelling for the vesicular GABA transporter. Following injection of biotin dextran amine into the central nucleus of the amygdala, anterogradely labelled axons and varicosities were found throughout the rostrocaudal extent of the nucleus of the solitary tract, particularly in the medial, ventral and ventrolateral subnuclei. The anterogradely labelled terminals were found to make predominantly symmetrical synaptic contacts with dendrites, and occasionally onto cell bodies and dendritic spines, and to contain immunoreactivity for GABA and for the vesicular GABA transporter. Immunolabelling of serial sections with antibodies to glutamate showed that none of these axon terminals contained high enough densities of gold particle labelling to suggest that they contained other than low metabolic levels of glutamate immunoreactivity. These results provide conclusive evidence for a GABAergic pathway from the central nucleus of the amygdala to the nucleus of the solitary tract. This GABAergic projection may provide a substrate for inhibition of lower brain stem visceral reflexes, including baroreflex inhibition, through which the central nucleus of the amygdala could participate in cardiovascular regulation related to emotional behaviour and the defence reaction.
The effect of a journal's prestige on readers' impressions of an article is unknown. Two hypotheses were tested: first, that attribution of a study to a "high" prestige journal would be associated with improved impressions and attribution to a "low" prestige journal would be associated with diminished impressions; and second, that formal training in epidemiology and biostatistics would mitigate the effects of this journal attribution bias. The study was designed as a trial among a random sample of 264 internists. Participants were asked to read an article and an abstract from either the Southern Medical Journal (SMJ) or the New England Journal of Medicine (NEJM). Questionnaires were constructed that either attributed the article or abstract to its source or presented it as unattributed. After each article or abstract, respondents were asked to rate the quality of the study, the appropriateness of the methodology employed, the significance of the findings, and its likely effects on their practice. A 20-point impression score was created based on responses to these statements. The effect of attribution to a specific journal and formal epidemiology training on impression scores were assessed using linear regression. Of the 399 eligible participants, 264 questionnaires were returned (response rate 66%). Differences in impression scores associated with attribution of an article or abstract to the NEJM were.71 [95% C.I. (-.44-1.87)] and.50 [95% C.I. (-.87-1.87)] respectively; differences in impression scores associated with attribution of an article or abstract to the SMJ were -.12 [95% C.I. (-1.53-1.30)] and -.95 [95% C.I. (-2.41-.52)]. A stratified analysis demonstrated that epidemiology training did not meaningfully alter the effect of journal attribution on participants' impression scores. If journal attribution bias exists, it is likely to exert small and clinically insignificant effects when physicians read articles carefully. Formal training in epidemiology and biostatistics does not appear to alter these results.
Purpose: 18F-Fluorodeoxyglucose-positron emission tomography (FDG-PET) is the superior imaging modality for detection of primary and recurrent colorectal cancer compared to magnetic resonance imaging (MRI) or computerized tomography (CT). We investigated the feasibility of developing intraoperative procedures for detection of FDG in tumor deposits in order to assist the surgeon in achieving an optimal reduction of tumor burden.Procedures: Fourteen patients (45-83 years of age) were scanned using FDG-PET followed by Gamma Detection Probe evaluation at laparotomy. One patient did not have a pre-operative FDG-PET scan. The collimated detector probe contained a CdZnTe crystal (7mm diameter x 2mm thick). We used a lower window setting of 200 KeV and an open upper window setting. Fasted patients were given an IV bolus of FDG (4.0-5.7 mCi) 15-20 minutes prior to preparation for surgery. Catheterization and the diuretic Lasix were used to remove FDG activity from the bladder. The time from FDG injection to intraoperative GDP data acquisition varied from 58-110 minutes.Results: In all patients, the GDP detected background activity in normal tissues (aorta, colon, liver, kidney, abdominal wall, mesentery, and urinary bladder). The GDP correctly identified single or multiple tumor foci in 13/14 patients as noted by an audible signal from the control unit (3 S.D. above counts obtained from normal tissues). These tumor foci corresponded to regions of high FDG uptake as seen on FDG-PET scans. The one case that the GDP did not localize was a recurrent mucin pseudomyxoma-producing tumor (acellular, mucinous deposits). Ex vivo GDP evaluations demonstrated significant tumor:normal adjacent tissue activity (audible signals in 6/6 tumor samples tested).Conclusions: These data demonstrate that tumors identified from pre-operative whole-body PET scans can be localized during surgery utilizing a gamma probe detector and FDG.
Damage to the lateral ligaments of the ankle, namely the anterior talofibular (ATFL) and the calcaneofibular (CFL) ligaments, is a frequently reported sports injury. The anterior drawer test is generally used to evaluate whether the ATFL has been torn, while the talar tilt test is used to determine if the CFL has been injured. Although these two manual tests are often utilized for quick diagnosis, they have been criticized because of their subjective nature and their inability to produce quantitative and reproducible results. A prototype ankle tester was manufactured that could measure the input force and torque, as well as the linear and angular deprivations for the anterior drawer test and the talar tilt test, respectively. This device was used to take readings on 10 human volunteers of a mean age of 21.6 years. This device was X-ray compatible, adjustable for varying patient sizes, relatively small, portable, and easy to operate. Testing was performed to determine how the stiffness of the ankle would respond to taping, and the effect of walking on the taped ankle. The overall mean anterior drawer was 5.93 mm and the mean talar tilt was 51.6 degrees for bare ankles using a force of 111 N (25 lbs) for the drawer and a torque of 16 N m for the tilt. Taping provided an average increase in stiffness of 11.3%, demonstrating that it did provide increased stability. However, statistically significant (P<0.05) decreases in the stiffness subsequent to taping were observed between the initially taped ankles and after 20 min of walking, when it was shown that talar tilt had increased. The prototype ankle tester produced repeatable measurements, and results show that the increase in stiffness due to taping did decrease after a short period of time.
We assessed the reading habits of internists with and without epidemiological training because such information may help guide medical journals as they make changes in how articles are edited and formatted. In a 1998 national self-administered mailed survey of 143 internists with fellowship training in epidemiology and study design and a random sample of 121 internists from the American Medical Association physician master file, we asked about the number of hours spent reading medical journals per week and the percentage of articles for which only the abstract is read. Respondents also were asked which of nine medical journals they subscribe to and read regularly. Of the 399 eligible participants, 264 returned surveys (response rate 66%). Respondents reported spending 4.4 hours per week reading medical journal articles and reported reading only the abstract for 63% of the articles; these findings were similar for internists with and without epidemiology training. Respondents admitted to a reliance on journal editors to provide rigorous and useful information, given the limited time available for critical reading. We conclude that internists, regardless of training in epidemiology, rely heavily on abstracts and prescreening of articles by editors.
Government agencies are usually interested in estimating the annual exploitation rate of a fish population for recreational and commercial fisheries. In this paper, we propose a model-based approach for the estimation of the exploitation rate. Our approach combines mark-recapture procedures with a creel survey (which is a type of angler survey). We consider moment estimation of the exploitation rate. We also consider estimation of the exploitation rate by stratifying the space-time units of the fisheries.
To design a temporal mandibular joint (TMJ), the designer should pay attention to the range of movement in the joint, the strength of the joint, and the size of the implant should conform, so that it does not hamper facial configuration. As a number of designs are available, in this study we have considered one of the most common and widely used implants for analysis. The main objective of this study is to examine the stress-strain behavior at the implant and what is happening at the implant bone interface. We have also examined whether implant material can be replaced by UHMWPE (ultra high molecular weight polyethylene) instead of titanium or Co-Cr-Mo alloy. Whether the change of positions of the screw used for fixation has any effect or not, we have modeled it considering actual shape and size, then divided it into number finite elements by using a FEM package. An appropriate surgical construct was modeled and loaded and studied for different parameters. We have shown that the metallic prostheses are good from a stress-strain point of view and UHMWPE cannot be used as such.
Research ethics is currently becoming the focus of attention as advancements in science are more in the public spotlight. Notoriety brings attention not only to the achievements, but to some of the more pressing issues that have risen to the surface in the debate on research ethics. Such issues include: conflicts of interest and industrial funding, research misconduct, and the need of ethics training for biomedical scientists.
The Christensen TMJ implant is often used clinically as a total joint replacement of the temporomandibular joint. The system consists of a thin fossa component and a condylar component with a polished articular head. In this study, we analyzed the surface finish and the metal structure of the components. We also measured the contact areas between the two components for different load levels. Such information may be useful in evaluating clinical performance as well as in making future improvements in the design of these implants.
BACKGROUND: The identification of lymph node metastases in colorectal resection specimens is necessary for accurate tumor staging. However, routine lymph node dissection by the pathologist yields only a subset of nodes removed surgically and may not include those nodes most directly in the path of lymphatic drainage from the tumor. Intraoperative mapping of such sentinel lymph nodes (SLNs) has been reported in cases of melanoma and breast cancer. We applied a similar method to cases of colorectal carcinoma, with emphasis on the pathology of the SLNs. METHODS: Eighty-three consecutive patients with colorectal carcinoma were evaluated after intraoperative injection of 1 to 2 mL of 1% isosulfan blue dye (Lymphazurin) into the peritumoral subserosa. Blue-stained lymph nodes were suture-tagged by the surgeon within minutes of the injection for identification by the pathologist, and a standard resection was performed. Designated SLNs were sectioned at 10 levels through the block; a cytokeratin immunostain (AE1) was also obtained. To evaluate the possibility that increased detection of metastases in the SLN might be solely due to increased histologic sampling, all initially negative non-SLNs in the first 25 cases were sectioned also at 10 levels. RESULTS: Sentinel lymph nodes were identified intraoperatively in 82 (99%) of 83 patients and accounted for 152 (11.9%) of 1275 lymph nodes recovered, with an average of 1.9 SLNs per patient. A total of 99 positive lymph nodes (38 positive SLNs and 61 positive non-SLNs) were identified in 34 node-positive patients. The SLNs were the only site of metastasis in 17 patients (50%), while 14 patients (41%) had both positive SLNs and non-SLNs. Three patients (9%) had positive non-SLNs with negative SLNs, representing skip metastases. In patients with positive SLNs, 91 (19%) of 474 total lymph nodes and 53 (12%) of 436 non-SLNs were positive for metastasis. In patients with negative SLNs, 8 (1%) of 801 total lymph nodes and 8 (1.2%) of 687 non-SLNs were positive for metastasis. Multilevel sections of 330 initially negative non-SLNs in the first 25 patients yielded only 2 additional positive nodes (0. 6%). All patients with positive SLNs were correctly staged by a combination of 4 representative levels through the SLN(s) together with a single cytokeratin immunostain. CONCLUSIONS: Intraoperative mapping of SLNs in colorectal carcinoma identifies lymph nodes likely to contain metastases. Focused pathologic evaluation of the 1 to 4 SLNs so identified can improve the accuracy of pathologic staging.
Levels of gangliosides in the plasma of human patients with cancers of the breast, cheek, oesophagus, rectum, penis, bladder and skin, as analysed by thin layer chromatography and quantitative densitometric scanning, were found to increase many fold (ranging from 3.5 to 5.96 folds), compared to that of normal individuals. The ganglioside levels in the plasma of patients with benign tumors were comparable to that of normal individuals, thus suggesting correlation between increased ganglioside levels in the plasma and malignant growth in cancer patients. These increased levels of gangliosides in the plasma of Ca-breast, Ca-cheek and Ca-penis gradually increased with the advancement of the disease and showed some correlation with the increase in stage of the disease. The levels of gangliosides in the plasma of patients with Ca-breast and Ca-cheek were found to decrease significantly after surgical removal of the primary cancerous growth. The results indicated diagnostic as well as prognostic significance of plasma ganglioside levels in human cancers.
This new blood test (leukergy) for infection is based on the fact that white cells agglomerate in peripheral blood of patients with inflammatory diseases. We evaluated leukergy in 25 children with proven septic arthritis of hip. It was found to be the efficient and earliest indicator of septic arthritis than the erythrocyte sedimentation rate (ESR), total leucocyte count (TLC), polymorphs and C-reactive protein (CRP). It also correlated well with the clinical severity of infection and the prognosis of disease. Thus leukergy is a simple, rapid and inexpensive slide test which was found as the best indicator profile for the presence of septic arthritis.
Plasma IgA level of Ehrlich ascites tumor bearing mice showed correlation with progress of tumor growth. In PAGE analysis total plasma IgA separated into 3 major bands corresponding to mol. wt. > or = 669,000 daltons, identical to 443,000 daltons and between 443,000 and 150,000 daltons. All the three bands increased gradually with progress of tumor growth upto day 14 and then declined on day 16. Total plasma IgA isolated by anti-IgA affinity chromatography when adoptively transferred to mice inhibited tumor growth. Affinity-purified plasma IgA separated into three major peak fractions after Sephadex G-200 column chromatography which corresponded with the bands of IgA on PAGE analysis. Three Sephadex G-200 IgA fractions when adoptively transferred to tumor-bearing mice showed effect different from total IgA. High mol. wt. IgA fraction (> or = 669,000 daltons) inhibited tumor growth whereas medium mol. wt. fraction (identical to 443,000 daltons) enhanced tumor growth. The low mol. wt. IgA fraction (< 443,000 and > 150,000 daltons) had no significant effect on tumor growth. The high mol. wt. IgA fraction enhanced tumor killing ability of peripheral blood lymphocytes (PBL) and peritoneal macrophages of tumor bearer in vitro. Medium mol. wt. IgA fraction inhibited tumor-killing ability of PBL in vitro but had no significant effect on peritoneal macrophages. The low mol. wt. IgA fraction showed a mild enhancing effect on tumor-killing ability of PBL but had no significant effect on peritoneal macrophages. The results established importance of IgA in tumor growth regulation and its therapeutic potentiality. The results indicated that tumor growth modulation by tumor plasma IgA is also mediated by its effect on cellular anti-tumor immune factors of the host.