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Biomedical subjects

M Hameed

Publications and source records attributed to M Hameed.

At least 19 recordsLinked to original sources

The effect of recombinant human growth hormone and resistance training on IGF-I mRNA expression in the muscles of elderly men.

The expression of two isoforms of insulin-like growth factor-I (IGF-I): mechano growth factor (MGF) and IGF-IEa were studied in muscle in response to growth hormone (GH) administration with and without resistance training in healthy elderly men. A third isoform, IGF-IEb was also investigated in response to resistance training only. The subjects (age 74 +/- 1 years, mean +/- S.E.M) were assigned to either resistance training with placebo, resistance training combined with GH administration or GH administration alone. Real-time quantitative RT-PCR was used to determine mRNA levels in biopsies from the vastus lateralis muscle at baseline, after 5 and 12 weeks in the three groups. GH administration did not change MGF mRNA at 5 weeks, but significantly increased IGF-IEa mRNA (237%). After 12 weeks, MGF mRNA was significantly increased (80%) compared to baseline. Five weeks of resistance training significantly increased the mRNA expression of MGF (163%), IGF-IEa (68%) and IGF-IEb (75%). No further changes were observed after 12 weeks. However, after 5 weeks of training combined with GH treatment, MGF mRNA increased significantly (456%) and IGF-IEa mRNA by (167%). No further significant changes were noted at 12 weeks. The data suggest that when mechanical loading in the form of resistance training is combined with GH, MGF mRNA levels are enhanced. This may reflect an overall up-regulation of transcription of the IGF-I gene prior to splicing.

Aged↗

Alveolar soft part sarcoma--reciprocal translocation between chromosome 17q25 and Xp11. Report of a case with metastases at presentation and review of the literature.

The molecular pathogenesis of alveolar soft part sarcoma, a rare tumor with uncertain histogenesis, was elucidated recently and was shown to be due to a translocation between chromosome 17q25 and Xp11 resulting in a fusion product between TFE3 (a transcription factor gene) at chromosome Xp11 and a novel gene designated as ASPL at chromosome 17q25. This results in the transcriptional dysregulation in the pathogenesis of this neoplasm. Of the 12 cases reported so far, the translocation was due to non-reciprocal translocation in 11 cases with only one case demonstrating a reciprocal translocation with respective fusion products. We report yet another case with reciprocal translocation between chromosomes 17q25 and Xp11 with TFE3/ASPL fusion product who presented with metastatic disease. A standard cytogenetic analysis of primary tumor cells with G-banding revealed an abnormal karyotype: 46, X, t(X;17)(p11;q25)[15]/46,XX[5]. PCR analysis of the frozen tumor tissue revealed a type 1 fusion product as described in the literature. We demonstrate a rare cytogenetic abnormality in ASPS, namely reciprocal translocation between chromosomes 17q25 and Xp11 with demonstration of molecular fusion product between TFE3 and ASPL in a patient who initially presented with pulmonary metastases.

Adult↗

Expression of IGF-I splice variants in young and old human skeletal muscle after high resistance exercise.

The mRNA expression of two splice variants of the insulin-like growth factor-I (IGF-I) gene, IGF-IEa and mechano growth factor (MGF), were studied in human skeletal muscle. Subjects (eight young, aged 25-36 years, and seven elderly, aged 70-82 years) completed 10 sets of six repetitions of single legged knee extensor exercise at 80 % of their one repetition maximum. Muscle biopsy samples were obtained from the quadriceps muscle of both the control and exercised legs 2.5 h after completion of the exercise bout. Expression levels of the IGF-I mRNA transcripts were determined using real-time quantitative RT-PCR with specific primers. The resting levels of MGF were significantly (approximately 100-fold) lower than those of the IGF-IEa isoform. No difference was observed between the resting levels of the two isoforms between the two subject groups. High resistance exercise resulted in a significant increase in MGF mRNA in the young, but not in the elderly subjects. No changes in IGF-IEa mRNA levels were observed as a result of exercise in either group. The mRNA levels of the transcription factor MyoD were greater at rest in the older subjects (P < 0.05), but there was no significant effect of the exercise bout. Electrophoretic separation of myosin heavy chain (MHC) isoforms showed the older subjects to have a lower (P < 0.05) percentage of MHC-II isoforms than the young subjects. However, no association was observed between the composition of the muscle and changes in the IGF-I isoforms with exercise. The data from this study show an attenuated MGF response to high resistance exercise in the older subjects, indicative of age-related desensitivity to mechanical loading. The data in young subjects indicate that the MGF and IGF-IEa isoforms are differentially regulated in human skeletal muscle.

Adult↗

Disaloganglioside GD2 loss following monoclonal antibody therapy is rare in neuroblastoma.

BACKGROUND: Gangliosicle GD2 is abundant on human neuroblastoma (NB). Monoclonal antibody 3F8 targeted to GD2 may have imaging and therapeutic potential. Antigen-negative clones can escape immune-mediated attack leading to clinical resistance or recurrence. PROCEDURE: Among 95 evaluable patients treated intravenously with 3F8 (94 Stage 4, 1 Stage 3), 66 received nonradiolabeled 3F8, 11 received 131-iodine-labeled-3F8 (8-28 mCi/kg) with autologous bone marrow rescue, and 18 received both forms of treatment. Prior to treatment, 90 patients tested positive for GD2 reactivity by bone marrow immunofluorescence (n = 68), tumor immunohistochemistry (n = 20), or diagnostic radioimmunoscintigraphy (n = 2). RESULTS: Of 62 patients who had refractory or recurrent neuroblastoma following 3F8 treatment, 61 (98%) tested positive for GD2 reactivity by bone marrow immunofluorescence (n = 51) or tumor immunohistochemistry (n = 10). The sole tumor that lost GD2 expression underwent phenotypic transformation into a pheochromocytoma-like tumor. CONCLUSIONS: The persistence of GD2 expression in refractory or recurrent NB suggests that complete antigen loss is an uncommon event and cannot account for treatment failure.

Antibodies, Monoclonal↗

Efficacy of follow-up evaluation in penetrating thoracic injuries: 3- vs. 6-hour radiographs of the chest.

Pneumothorax (PTX) in patients with penetrating thoracic trauma is routinely ruled out with serial chest radiographs (CXRs). This study examined the efficacy of a shortened time period between initial and follow-up radiographs. Patients with penetrating torso injuries treated at a Level-1 trauma center received a CXR during their initial evaluation. If no pneumothorax or hemothorax was noted, and the patient did not require immediate admission to the Intensive Care Unit or operating room, a repeat chest film was taken at 3 and 6 h. Findings were treated as clinically indicated, and patients were discharged home if the last radiograph revealed no evidence of pathology. Over a 15-month period, 116 patients were evaluated for penetrating thoracic injuries (93 stabbings, 23 gunshot wounds) and had no pneumothorax detected on initial CXR. Two patients had pneumothorax detectable only by computed tomography. One patient had a normal initial CXR, but developed a PTX on the 3-h film, requiring tube thoracostomy. No patients developed a PTX on the 6-h study that was not present on the initial or 3-h CXR. In conclusion, extending the time between initial and final CXRs to 6 h in patients with penetrating thoracic trauma provided no additional information that was not available on the 3-h film.

Follow-Up Studies↗

Human papillomavirus typing in HIV-positive women.

OBJECTIVE: Human papillomavirus (HPV) is the major cause of cervical carcinoma and cervical intraepithelial neoplasia worldwide. Certain HPV types have a strong association with and probably a causative role in the pathogenesis of premalignant cervical lesions. Epidemiologic studies in women infected by the human immunodeficiency virus (HIV) have shown an increased incidence of squamous intraepithelial lesions (SILs), which were predominantly high-grade. Six to 30 per cent of women diagnosed with atypical squamous cells of undetermined significance (ASCUS) on a Papanicolaou (Pap) smear harbor SIL in normal screening populations. This study was undertaken to determine the presence of low-and high-risk HPV types in women infected by HIV and to correlate the results to those of the Pap smear. STUDY DESIGN: HPV DNA typing (low- and high-risk) by Digene (Digene Corporation, Gathesburg, MD) hybrid capture methodology was performed on cervical swabs from 209 HIV-positive women. The results of HPV typing were correlated with those of the Pap smear in a retrospective analysis. RESULTS: One hundred and one women (48%) tested positive for HPV subtypes by DNA typing by the hybrid capture method. Of these, 64 patients (63%) had Pap smears which were read as being normal, having benign cellular changes, or having ASCUS (favor reactive process). Of these, 19 patients tested positive for both high-risk and low-risk subtypes, 32 patients tested positive only for high-risk subtypes, and 13 patients tested positive only for low-risk subtypes. CONCLUSION: HPV subtyping identifies a significant group of HIV-positive women who are at risk for developing cervical intraepithelial neoplasia, although they may not show significant abnormalities on their Pap smears.

DNA, Viral↗

Tumefactive fibroinflammatory lesion of the neck with progressive invasion of the meninges, skull base, orbit, and brain.

SUMMARY: Tumefactive fibroinflammatory lesions of the head and neck are rare. CNS involvement has not been reported. We present a histologically proven case of a tumefactive fibroinflammatory lesion that originated in the left side of the neck and progressed over 2 years to involve the meninges, the cavernous sinuses, the right temporal lobe, and the right orbit. The lesion caused destruction of the skull base and a subdural hematoma. The relationship of the present lesion to idiopathic hypertrophic pachymeningitis and Tolosa-Hunt syndrome is discussed.

Adult↗

The 4q-Syndrome.

The 4q-Syndrome: Here we report four cases of interstitial and terminal deletions of the long arm of chromosome 4. Case 1 is a 16 month old boy with del(4)(q12q21) who has soft dysmorphic features, tetralogy of Fallot, and severe developmental delay. Case 2 is a male infant with the same deletion and congenital cardiomyopathy. He suffered severe birth asphyxia and died at the age of 6 months. His father was found to have a complex chromosome 4 rearrangement. Case 3 is a female infant with del(4)(q33) who died of aspiration pneumonia. She was mildly dysmorphic and presented with heart failure and hypercalcaemia. Case 4 is a 8 month old girl who has del(4)(q33) and Pierre-Robin sequence. So far about 70 patients with microscopically visible deletions of chromosome 4q have been described. Although they vary in their phenotypes, they have several features in common. We suggest to use the term 4q-syndrome for all macrodeletions of the long arm of chromosome 4.

Abnormalities, Multiple↗

Increased expression of preprotachykinin-I and neurokinin receptors in human breast cancer cells: implications for bone marrow metastasis.

Neuropeptides are implicated in many tumors, breast cancer (BC) included. Preprotachykinin-I (PPT-I) encodes multiple neuropeptides with pleiotropic functions such as neurotransmission, immune/hematopoietic modulation, angiogenesis, and mitogenesis. PPT-I is constitutively expressed in some tumors. In this study, we investigated a role for PPT-I and its receptors, neurokinin-1 (NK-1) and NK-2, in BC by using quantitative reverse transcription-PCR, ELISA, and in situ hybridization. Compared with normal mammary epithelial cells (n = 2) and benign breast biopsies (n = 21), BC cell lines (n = 7) and malignant breast biopsies (n = 25) showed increased expression of PPT-I and NK-1. NK-2 levels were high in normal and malignant cells. Specific NK-1 and NK-2 antagonists inhibited BC cell proliferation, suggesting autocrine and/or intercrine stimulation of BC cells by PPT-I peptides. NK-2 showed no effect on the proliferation of normal cells but mediated the proliferation of BC cells. Cytosolic extracts from malignant BC cells enhanced PPT-I translation whereas extracts from normal mammary epithelial cells caused no change. These enhancing effects may be protein-specific because a similar increase was observed for IL-6 translation and no effect was observed for IL-1alpha and stem cell factor. The data suggest that PPT-I peptides and their receptors may be important in BC development. Considering that PPT-I peptides are hematopoietic modulators, these results could be extended to understand early integration of BC cells in the bone marrow, a preferred site of metastasis. Molecular signaling transduced by PPT-I peptides and the mechanism that enhances translation of PPT-I mRNA could lead to innovative strategies for BC treatments and metastasis.

Benzamides↗

Splenic smooth-muscle tumors in children with acquired immunodeficiency syndrome: report of two cases of this unusual location with evidence of an association with Epstein-Barr virus.

Smooth-muscle neoplasms are rarely located in the spleen. They have been previously reported in five cases of children with human immunodeficiency virus (HIV) infection/acquired immunodeficiency syndrome (AIDS). Two cases of children with HIV infection/AIDS with autopsy and surgical pathology evidence of multiple smooth-muscle neoplasms with splenic involvement are presented. DNA was extracted from histology slides in both cases for analysis for Epstein Barr (EB) virus. In both cases, the presence of EB virus was confirmed. This paper documents two additional cases of the unusual phenomenon of splenic involvement by smooth-muscle neoplasms in the setting of AIDS in childhood and further supports the role of EB virus in the development of these neoplasms.

Acquired Immunodeficiency Syndrome↗

C282Y mutation and hepatic iron status in hepatitis C and cryptogenic cirrhosis.

BACKGROUND: Increased iron deposition in liver is seen in both primary and secondary hemochromatosis. However, it is not uncommon to see significant iron deposition in a liver biopsy, explant, or autopsy specimen without any significant clinical risk factor. Because of the discovery of the candidate gene (HFE) for hereditary hemochromatosis, we may now be able to screen high-risk patient populations for the abnormal mutation (C282Y). MATERIALS AND METHODS: In this study we analyzed the livers of 50 transplant patients with a diagnosis of either hepatitis C cirrhosis or cryptogenic cirrhosis for the prevalence of the more common C282Y mutation of the HFE gene and correlated the findings to hepatic iron concentration. RESULTS: Of the 26 cases of hepatitis C cirrhosis, 3 were found to be heterozygous for the C282Y mutation. Of the 22 cases of cryptogenic cirrhosis, 1 was found to be heterozygous for the C282Y mutation. Stainable iron was increased in hepatitis C cirrhosis (76.9%) as compared to cryptogenic cirrhosis (50%) (P =. 05). Of the 3 heterozygotes with hepatitis C cirrhosis, 2 showed hepatic iron concentrations of 3+ and 4+, and 1 showed 1+. CONCLUSIONS: We conclude that patients with hepatitis C have an increased tendency to accumulate iron in the liver, and mutations in the HFE gene play a minor role in hepatic accumulation of iron in these patients.

Amino Acid Substitution↗

Pregnancy-associated invasive squamous cell carcinoma of the vulva in a 28-year-old, HIV-negative woman. A case report.

BACKGROUND: The incidence of invasive squamous cell carcinoma of the vulva in women under 40 years of age has been increasing, particularly in association with human papillomavirus. Invasive vulvar carcinoma is rare in women under 30, as is an association with pregnancy. We report on a 28-year-old woman who was diagnosed with invasive squamous cell carcinoma of the vulva during pregnancy. CASE: The patient, gravida 5, para 4105, HIV negative, presented to the emergency room with vulvar pain. She had delivered a term infant three months earlier at another institution and was diagnosed with squamous cell carcinoma of the vulva at that time. At this admission, a 4.0-cm, ulcerated lesion involving the left labium minus was noted. The patient underwent examination under anesthesia with bilateral inguinal lymph node dissection, cone biopsy, radical vulvectomy and excision of perianal lesions. CONCLUSION: This case demonstrates the need to biopsy all suspicious vulvar lesions, even in young and pregnant women.

Adult↗

Sudden death in a child due to an intrathoracic paraganglioma.

A 12-year-old boy under treatment for asthma was found dead in his home. The autopsy revealed a large posterior mediastinal mass that completely compressed the upper lobe of the right lung and the associated airways. This mass extended from the right costovertebral sulcus into the thoracic spinal canal through the spinal foramen and compressed the spinal cord. It was located in the epidural space and was adherent to a nerve root. The histologic and immunocytochemical features were that of a paraganglioma. Although neurogenic tumors are the most common posterior mediastinal masses in the pediatric population, paragangliomas are rare, and spinal involvement has not been described in children. In addition, sudden death has not been reported in association with any of the 13 cases of posterior mediastinal paraganglioma described in the literature as involving the spine. This case illustrates an unusual cause of sudden death in a pediatric patient due to a benign neoplasm.

Asthma↗

Use of rapid dipstick tests to exclude urinary tract infection in children.

Children presenting with symptoms attributable to urinary tract infection (UTI) are not uncommonly referred to paediatric departments for assessment. The aim of this study was to evaluate the use of rapid dipstick tests in the diagnosis of urinary tract infection in children. Urine was collected from 375 children admitted to a general paediatric ward, in whom UTI was a possibility on clinical grounds. Of these, 124 were less than one year old. Urine was tested with a dipstick for the presence of nitrite and leucocyte esterase. Bacterial culture and examination for white cells, red cells and other formed elements were performed. The results of the dipstick tests, microscopy and culture were correlated with the clinical details. Combination of a negative dipstick test for nitrite and leucocyte esterase showed a negative predictive value for UTI of 96.9% and a specificity of 98.7%. In children less than a year old these values were 96.7% and 99.2% respectively. The leucocyte esterase strip test showed a negative predictive value for pyuria of 94.3% with a specificity of 86.9%. In children less than a year old these values were 93.1% and 84.4% respectively. The use of dipsticks for the detection of urinary nitrate and leucocyte esterase in daily clinical practice is recommended. In children, the absence of both nitrite and leucocyte esterase in urine indicates that UTI is unlikely; however, positive dipstick tests for nitrite and/or leucocyte esterase are not specific indicators of UTI, and should not be used in place of laboratory examination. The dipstick method is most likely to be useful as a screening test to exclude UTI in children, but may be less suitable for infants. It should not be used to diagnose urinary tract infection.

Adolescent↗

Disialoganglioside G(D2) loss following monoclonal antibody therapy is rare in neuroblastoma.

Ganglioside GD2 is abundant on human neuroblastoma (NB). Monoclonal antibody 3F8 targeted to GD2 may have imaging and therapeutic potential. Antigen-negative clones can escape immune-mediated attack, leading to clinical resistance or recurrence. Among 95 evaluable patients treated i.v. with 3F8 (94 stage 4 and 1 stage 3), 66 received nonradiolabeled 3F8, 11 received 131I-labeled 3F8 (8-28 mCi/kg) with autologous bone marrow rescue, and 18 received both forms of treatment. Prior to treatment, 91 patients tested positive for GD2 reactivity by bone marrow immunofluorescence (n = 68), tumor immunohistochemistry (n = 20), or diagnostic radioimmunoscintigraphy only (n = 3). Of 62 patients who had refractory or recurrent NB following 3F8 treatment, 61 (98%) tested positive for GD2 reactivity by bone marrow immunofluorescence (n = 51) or tumor immunohistochemistry (n = 10). The sole tumor that lost GD2 expression underwent phenotypic transformation into a pheochromocytoma-like tumor. The persistence of GD2 expression in refractory or recurrent NB suggests that complete antigen loss is an uncommon event and cannot account for treatment failure.

Antibodies, Monoclonal↗

Fine-needle aspiration of anaplastic thyroid carcinoma with varied cytologic and histologic patterns: a case report.

Anaplastic carcinoma of the thyroid (ACT) is a rare subtype of thyroid neoplasm. This tumor represents approximately 5-10% of all thyroid malignancies and its poor prognosis has not changed in 25 years. ACT often arises in a long-standing thyroid nodule and has been documented to be associated with a variety of more well-differentiated thyroid carcinomas. We describe the cytologic features of a case in which the patient had a 10-yr history of a thyroid nodule. The ACT in this case had a cytologic and histologic appearance of several different subtypes of thyroid carcinomas.

Aged↗

Abnormal insulin and glucose metabolism in the JCR:LA-corpulent rat.

The JCR:LA-corpulent rat, if homozygous for the cp gene, exhibits a syndrome characterized by obesity, hypertriglyceridemia, and hyperinsulinemia with impaired glucose tolerance. The insulin and glucose metabolism of lean and obese rats of this strain have been studied with the euglycemic insulin clamp technique in 3- and 9-month-old rats. Lean rats require a twofold greater glucose infusion rate than obese rats at high plasma insulin concentrations. Glucose turnover was measured using isotope dilution techniques and 1-3H-glucose. Glucose turnover in lean rats of both sexes increases by a factor of 2 to 3 at very high insulin levels. In contrast, obese male rats are unable to respond even to extreme insulin levels with an increase in basal glucose turnover, indicating a profound insulin resistance. The calculated hepatic glucose production is inhibited by high insulin levels in the obese male rats, while lean animals show no inhibition. Thus, the obese male rats have normal basal glucose turnover, but have a profound insulin insensitivity in peripheral tissues. These abnormalities are present at a much reduced level in the obese female rats. These results are consistent with the hypothesis that the hyperinsulinemia, which correlates strongly with cardiovascular disease in this strain of rat, is secondary to a marked peripheral insulin resistance.

Aging↗