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Biomedical subjects

S H Khan

Publications and source records attributed to S H Khan.

At least 19 recordsLinked to original sources

Pattern of local relapse of maxillary sinus carcinoma.

Maxillary sinus carcinoma (MSC) is a rare disease with a variety of treatment options. The present study was undertaken to review the outcome of patients with treated MSC in order to clarify the factors related to local recurrence by analyzing CT findings. The study group comprised of 47 cases, 40 males and 7 females with a median age of 61 years (range, 40- 84 years) treated between 1988 to 1996 at the department of radiotherapy. CT was taken with a slice thickness of 5 mm and contrast material was routinely used. The mean follow-up period for the group was 45.0 months (range, 3-125 months). The treatment policy was either preoperative radiotherapy of 40Gy/16fr followed by maxillectomy or radical radiotherapy of 65Gy/26fr with partial maxillectomy during the course of radiotherapy. By using CT-simulation, wedge pair techniques were used in most patients with Cobalt or 6MV X-ray machines as treatment sources. Tumor extension was categorized into the following anatomical sites: orbital contents, other paranasal sinuses, posterior wall of the maxillary sinus, pterygoid plate/muscle, nasopharynx, infra-temporal fossa, base of the skull, anterior wall of the maxillary sinus, subcutaneous tissue, cheek mucosa, hard palate and alveolar bone. Local control was computed by using the Kaplan-Meier method and p value was measured by using Chi-squared test. The 5-year overall local control rates for all patients were 56%. The local recurrence was found in 19 of 47 patients (40.4%). Tumors extending to pterygoid plates (n=13) and pterygoid muscles (n=10) showed higher rate of local recurrences as compared to those without extensions (9/13 [69%] vs 10/34 [29%], p<0.02 and 7/10 [70%] vs 12/37 [32%], p<0.05, respectively). Extensions to nasopharynx (6/9, 66%) and base of skull (4/6, 66%) also showed higher rates of recurrence; however, those were not statistically significant. More than 80% of the relapse became manifest within 12 months of diagnosis and isolated local failure was the most common pattern. This analysis indicates that tumor extension to pterygoid plate/muscles, results in higher rates of recurrences. This may due to the difficult surgical accessibility of the tumor. During radiotherapy planning, special emphasis should be given to this sites of tumor extension to avoid possible local recurrence.

Adult↗

Expression of FGFR-2 and FGFR-3 in the normal human fetal orbit.

AIMS: To demonstrate the expression patterns of two fibroblast growth factor receptors (FGFR-2 and FGFR-3) in the normal human fetal orbit. METHODS: 6 microm orbital slide sections were prepared from 12 week old human fetal material obtained within established ethical guidelines. Radioactive in situ hybridisation techniques were used to demonstrate the expression patterns of FGFR-2 and FGFR-3 within these sections. Only one foetus had appropriate orbital sections taken. RESULTS: FGFR-2 was expressed within the extraocular muscles (EOMs) and the optic nerve sheath and to a lesser degree within the orbital periosteal margins and the cranial sutures. FGFR-3 was expressed a lot within the periosteal margins and cranial sutures but not within either the EOMs or the optic nerve sheath. CONCLUSIONS: FGFR-2 and FGFR-3 are differentially expressed within different orbital components. FGFR-2 gene mutations may be responsible for craniosynostotic syndromes such as Crouzon, Pfeiffer, and Apert, while those in the FGFR-3 gene may cause isolated unicoronal synostosis. EOMs may be histologically abnormal in cases of Apert, Pfeiffer, and Crouzon syndromes but not isolated unicoronal synostosis. The pattern of expression of FGFR-2 in the normal human fetal orbit may explain some of the EOM histological findings seen in some cases of Apert, Pfeiffer, and Crouzon syndromes.

Fibroblast Growth Factor 2↗

Antiischemic effects of topiramate in a transient global forebrain ischemia model: a neurochemical, histological, and behavioral evaluation.

The mechanisms of action of the anticonvulsant topiramate (TPM) are indicative of a potential benefit during cerebral ischemia. TPM was studied in a transient global forebrain ischemia (TGFI) model in gerbils in which 40 mg/kg was administered before or after TGFI. Control groups were administered 0.9% normal saline similarly. The evaluation consisted of neurochemical, histological, and functional analyses. The data obtained indicates that unlike the focal cerebral ischemia model, TPM is not neuroprotective in TGFI. The difference in effect, which may be due to the difference in species or the type of ischemia, points to the need for caution when extrapolating animal data from this drug to humans.

Animals↗

Visual outcomes and amblyogenic risk factors in craniosynostotic syndromes: a review of 141 cases.

AIMS: To determine the visual outcome and prevalence of amblyogenic risk factors in children with craniosynostotic syndromes. METHODS: The case notes of 141 children seen within the craniofacial unit were reviewed and information retrieved on date of birth, age at first and last examination, cycloplegic refraction at last visit, best corrected visual acuity at last visit, horizontal ocular deviation in primary position at first visit, and alphabet pattern if any. The presence of astigmatism, its magnitude, and orientation of axis were determined. RESULTS: 40.3% of patients had 1 dioptre (D) of astigmatism or greater and, of these, 64% had oblique astigmatism in at least one eye. Anisometropia of 1D or more was found in 18% of patients (age matched normals 3.5%). Horizontal strabismus was found in 70% (38% exotropia, 32% esotropia). Visual outcome results showed 39.8% of patients (45 of 113) had visual acuity of 6/12 or worse in their better eye. CONCLUSION: In the largest study to date a poor visual outcome was shown in children with Crouzon's, Pfeiffer's, Apert's, and Saethre-Chotzen syndromes (39.8% with 6/12 or worse in the better eye) together with significant prevalence of amblyogenic risk factors.

Adolescent↗

The technique of intracerebral microdialysis.

Intracerebral microdialysis is an increasingly popular experimental technique. A brief description of the principles of microdialysis is presented and the terms relevant to the procedure are defined. The methodology involved in conducting intracerebral microdialysis is described in detail. Factors influencing the outcome of analysis such as external stimuli, perfusion fluid, perfusion rate, temperature, probe placement, membrane characteristics, and timing of sample collection are discussed. The importance of maintaining the uniformity of the above-mentioned factors is stressed.

Animals↗

Evaluation of an optimal temperature for brain storage in delayed 2, 3,5-triphenyltetrazolium chloride staining.

This paper presents the determination of an optimal temperature for delayed 2,3,5-triphenyltetrazolium chloride (TTC) staining. Twenty-one rats were subjected to right middle cerebral artery embolic stroke and sacrificed 96 h following ischemia. The brains were harvested and stained immediately after sacrifice or stored for 8 h at 21-23 degrees C or 4 degrees C, respectively. The stained sections were scanned and infarct volume calculated. The quality of staining, distinction of borders between infarcted and non-ischemic tissue and ease of differentiating ischemic tissue in colored and grayscale images was assessed. The present study indicates that results of TTC obtained immediately after animal sacrifice, or delayed TTC staining while storing the brains at room temperature or 4 degrees C are comparable.

Animals↗

Differential requirement for p19ARF in the p53-dependent arrest induced by DNA damage, microtubule disruption, and ribonucleotide depletion.

p19ARF has been implicated as a key regulator of p53 stability and activation. While numerous stresses activate the p53 growth arrest pathway, those requiring p19ARF remain to be elucidated. We used p19ARF knockout mouse embryo fibroblasts to show that DNA damage and microtubule disruption require p19ARF to induce p53 responses, whereas ribonucleotide depletion and inhibition of RNA synthesis by low doses of actinomycin D do not. The data provide evidence that the arrest pathway activated by ribonucleotide depletion involves some different signal transducers than those activated by DNA damage or microtubule disruption. We also present biochemical analyses that provide insights into the mechanism by which p53 and p19ARF cooperate in normal cells to induce cell cycle arrest.

Animals↗

The role of taurine in neuronal protection following transient global forebrain ischemia.

Osmoregulation and post ischemic glutamate surge suppression (PIGSS) are important mechanisms in the neuroprotective properties of taurine. We studied the role of taurine in PIGSS following transient global forebrain ischemia (TGFI). A group of gerbils received a high dose of continuous intracerebral taurine during the peri-ischemic period. Beta-alanine was given similarly to a negative control group. The control group consisted of animals undergoing only TGFI. On the fourth day following commencement of drug administration, TGFI was induced. Concurrently, half the animals from each group receiving an agent had intracerebral microdialysis. All animals underwent histological assessment at day 7. The microdialysis and histological data was analyzed. Our results showed that taurine treatment did not cause PIGSS. The histological difference between the three groups was statistically insignificant. We conclude that intracerebral taurine in the dosage administered during peri-ischemic period, does not result in PIGSS or histologically evident neuroprotection.

Animals↗

Tibial plateau fractures. A new classification scheme.

Fractures of the tibial plateaus are common injuries. Various classification schemes have been used to describe these injuries. Although each system has its own purpose, the simpler systems do not allow comparison with more complex divisions. The problem is compounded by the variable use of adjectives that describe these fractures. A comprehensive classification of tibial plateau fractures should group fractures that are similar in topography, morphology, and pathogenesis, requiring similar treatment, and having a similar prognosis. Fracture dislocations and standard tibial plateau fractures should be incorporated into a single classification to avoid the use of two complementary classifications. Any such classification should not be difficult to remember or to use. Keeping in mind these requirements, the authors devised a simple yet comprehensive classification. The authors studied 80 cases of tibial plateau fractures from January 1988 to September 1997, and used contemporary classifications of tibial plateau fractures as a database to formulate the new classification. A new fracture, subcondylar bicondylar with coronal split, has been classified for the first time. An alphanumeric system has been developed that has made nomenclature easy to remember and use. An effort has been made to address the profoundly confusing issue of variable adjectives that describe these injuries. A review of the literature shows that fractures in the authors' classification have been grouped according to similar pathomechanics, treatment, and functional results.

Adult↗

p53 regulation by post-translational modification and nuclear retention in response to diverse stresses.

p53 activation by diverse stresses involves post-translational modifications that alter its structure and result in its nuclear accumulation. We will discuss several unresolved topics regarding p53 regulation which are currently under investigation. DNA damage is perhaps the best-studied stress which activates p53, and recent data implicate phosphorylation at N-terminal serine residues as critical in this process. We discuss recent data regarding the potential kinases which modify p53 and the possible role of the resulting phosphorylation events. By contrast, much less is understood about agents which disrupt the mitotic spindle. The cell cycle phase, induction signal, and biochemical mechanism of the reversible arrest induced by microtubule disruption are currently under investigation. Finally, a key event in response to any genotoxic stress is the accumulation of p53 in the nucleus. The factors which determine the steady state level of p53 are starting to be elucidated, but the mechanisms responsible for nuclear accumulation and nuclear export remain controversial. We discuss new studies revealing a mechanism for nuclear retention of p53, and the potential contributions of MDM2 to this process.

Animals↗

Identification of a novel circular single-stranded DNA associated with cotton leaf curl disease in Pakistan.

Recent reports have suggested that cotton leaf curl virus (CLCuV), a geminivirus of the genus Begomovirus, may be responsible for cotton leaf curl disease in Pakistan. However, the causal agent of the disease remains unclear as CLCuV genomic components resembling begomovirus DNA A are unable to induce typical disease symptoms when reintroduced into plants. All attempts to isolate a genomic component equivalent to begomovirus DNA B have been unsuccessful. Here, we describe the isolation and characterisation of a novel circular single-stranded (ss) DNA associated with naturally infected cotton plants. In addition to a component resembling DNA A, purified geminate particles contain a smaller unrelated ssDNA that we refer to as DNA 1. DNA 1 was cloned from double-stranded replicative form of the viral DNA isolated from infected cotton plants. Blot hybridisation using probes specific for either CLCuV DNA or DNA 1 was used to demonstrate that both DNAs co-infect naturally infected cotton plants from different geographical locations. DNA 1 was detected in viruliferous Bemisia tabaci and in tobacco plants infected under laboratory conditions using B. tabaci, indicating that it is transmitted by whiteflies. Sequence analysis showed that DNA 1 is approximately half the size of CLCuV DNA but shares no homology, indicating that it is not a defective geminivirus component. DNA 1 has some homology to a genomic component of members of Nanoviridae, a family of DNA viruses that are normally transmitted by aphids or planthoppers. DNA 1 encodes a homologue of the nanovirus replication-associated protein (Rep) and has the capacity to autonomously replicate in tobacco. The data suggest that a nanovirus-like DNA has become whitefly-transmissible as a result of its association with a geminivirus and that cotton leaf curl disease may result from a mutually dependent relationship that has developed between members of two distinct DNA virus families that share a similar replication strategy.

Amino Acid Sequence↗

Mechanisms involved in the potentiation of melphalan by the bioreductive compound THNLA-1 in vitro.

9-[3-(2-Nitro-1-imidazolyl)propylamino]-1,2,3,4-tetrahydroacridine hydrochloride (THNLA-1) is a 2-nitroimidazole-based, weakly DNA-intercalating bioreductive agent that significantly potentiates the toxic effects of commonly used antitumor drugs such as melphalan (L-PAM) or cis-DDP in sensitive or resistant cell lines in culture, as well as in solid tumors in mice. Potentiation in vitro was observed when cells were preexposed to THNLA-1 under hypoxic conditions before exposure to L-PAM under aerobic conditions. In this study we investigated possible mechanisms involved in the potentiation of L-PAM by THNLA-1 in V79 Chinese hamster cells. Limited depletion of glutathione with buthionine sulfoximine or THNLA-1 under hypoxic pretreatment conditions accounted for only 8.3% of the potentiation induced by THNLA-1. However, DNA, RNA, and protein synthesis were inhibited in a synergistic way in cells preexposed to THNLA-1 under hypoxic conditions (2 h, 37 degrees C) and then coexposed to various doses of L-PAM under aerobic conditions (1 h, 37 degrees C). Cell cycle analysis by flow cytometry showed a slow traverse through the S phase in the L-PAM-alone-treated cells. However, this phenomenon was more prominent in the THNLA-1 plus L-PAM-treated cells. Under aerobic co-incubation conditions with L-PAM, no difference was observed in the cell cycle of L-PAM-alone-treated cells vs. THNLA-1 plus L-PAM-treated cells. Significantly increased apoptosis was observed in the hypoxia-pretreated cells with THNLA-1, 12 and 24 h posttreatment. Comet and alkaline elution assay analysis showed increased DNA cross-links in the hypoxia-pretreated cells with THNLA-1 compared to the L-PAM-alone-treated cells. Finally, potential lethal damage repair was totally suppressed only in the hypoxia-pretreated cells with THNLA-1. In conclusion, DNA damage and hindrance in its repair are the most important mechanisms in the potentiation of L-PAM by THNLA-1, under hypoxic pretreatment conditions.

Animals↗

p53 and pRb prevent rereplication in response to microtubule inhibitors by mediating a reversible G1 arrest.

Cell cycle checkpoints are safeguards that ensure the initiation of downstream events only after completion of upstream processes. The tumor suppressors p53 and pRb prevent initiation of a second round of replication in response to spindle inhibitors, but it has yet to be proven that this is a mitotic checkpoint response. We show that asynchronous human fibroblasts arrest in G1 with 4 N DNA content after nocodazole treatment, whereas isogenic p53- and pRb-deficient fibroblasts rereplicate. Importantly, nocodazole elicits a reversible arrest in G0-G1 synchronized normal human fibroblasts but not in isogenic p53-deficient derivatives. Furthermore, the G1 cyclin-dependent kinase inhibitors p21 and p16 also play critical roles in limiting rereplication. Hence, p53 and pRb are required during G1 to prevent entry into a replicative cycle and appear to provide a connection between the structural integrity of the microtubules and the cell cycle machinery in interphase cells.

Aneuploidy↗

Comparison of percutaneous ventriculostomies and intraparenchymal monitor: a retrospective evaluation of 156 patients.

Intraventricular catheters (IVC) and Intraparenchymal fiberoptic catheters (IPC) are the prevalent methods of intracranial pressure (ICP) monitoring. This study assesses the complications caused by either method. Previous studies have shown a higher complication rate with IVC. In 156 consecutive patients, with IVC (n = 104) or IPC (n = 52) insertion, the demographics, Glasgow coma score (GCS), ICP, duration of monitoring, changes in monitoring device, complications and computerized tomography findings, were recorded. The patients were categorized into severe (GCS 3-8), moderate (GCS 9-12) and mild (GCS 13-15) groups. A retrospective, comparative analysis of both techniques was conducted, using Kruskal-Wallis one way analysis of variance with chi square approximation and Mann-Whitney U tests. The use of IPC at 86.5% predominated in patients with GCS 3-8, while IVC at 81.4% and 92% prevailed in GCS groups 9-12 and 13-15, respectively (p = 0.000). 43.2% IVC were used for 10+ days and 25.9% for 1-3 days, while 80% of IPC were used for less than 6 days (p = 0.000). The complication rate for IVC and IPC was 25% vs 4.4% (p = 0.000). The infection rate was 4.4% and 0.6% (p = 0.1) while, inadvertent removal 4.4% vs 1.2% (p = 0.4), respectively. Malpositions occurred only with IVC (20.1%). All documented complications were without untoward clinical sequelae. We conclude that, IVC remains comparable to IPCs in complications.

Adolescent↗

In-situ hybridization localized MUC7 mucin gene expression to the mucous acinar cells of human and MUC7-transgenic mouse salivary glands.

MUC7 gene that encodes the low molecular weight human salivary mucin MG2, was previously shown to be expressed in tissue-specific manner in normal human salivary glands and in salivary glands of transgenic mice carrying the MUC7 transgene. The purpose of this study was to examine the cell specificity of MUC7 expression in human and transgenic mice salivary glands. To localize the MUC7 transcripts, we used in-situ hybridization in combination with Tyramide Signal Amplification procedure. The results clearly showed that in both the human and transgenic mice salivary gland tissue sections, MUC7 transcripts were localized only in mucous acinar cells; no signals were found in serous acinar cells or any other cell types present in these salivary glands.

Animals↗

Training and retaining Shasthyo Shebika: reasons for turnover of community health workers in Bangladesh.

Shasthyo Shebikas (SS) are community health workers forming the core of BRAC's Essential Health Care (EHC) programme. The SS dropout was 44 percent for study area and 32 percent for EHC programme. The SS discontinued their work due to lack of time, lack of "profit", and family's disapproval. The effects of the dropouts were decreased achievement of targets, and a loss of money in the amount of $24 (U.S.) per dropout SS for their training and supervision. The SS retention may increase if EHC strictly adheres to its existing guidelines when selecting trainees, and if it highlights during SS training that SS; s first and foremost role will be as that of a volunteer and then of a salesperson.

Allied Health Personnel↗