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Biomedical subjects

K Ahmad

Publications and source records attributed to K Ahmad.

At least 19 recordsLinked to original sources

Presence of expression products of c-erbB-1 and c-erbB-2/HER2 genes on mammalian sperm cell, and effects of their regulation on fertilization.

The present study was conducted to investigate the presence of expression products of c-erbB-1 and c-erbB-2/HER2 genes on mammalian sperm cell, and study the effects of their antibodies on fertilization. The mature sperm cells from various mammalian species (human, mouse, rabbit and rat) were found to have EGF-receptors but not the p185HER2 molecules by indirect immunofluorescence technique (IFT) and Western blot procedure. Though the EGF-receptors present on sperm cells were functionally active and responded to ligand binding, their activation by EGF or blocking by antibodies did not affect the sperm cells in acquiring their fertilization potential. These results indicate that the products of c-erbB-1 and c-erbB-2/HER2 genes, though they have been shown to have tyrosine kinase enzyme activity, do not seem to play a major role in the development of the fertilizing capacity of sperm cells.

Amino Acid Sequence

Neutron therapy in Saudi Arabia: an overview and results of dose searching study in head and neck cancer.

The King Faisal Specialist Hospital and Research Centre is the only center in the Middle East that incorporates a neutron therapy facility. The neutron beam is produced by a cyclotron, which produces a beam by either a (d(15)+Be) or (p(26)+Be) reaction. The beam from the proton reaction is selected for therapy because of its superior physical characteristics. These were verified by an intercomparison conducted by the European Organization for Research on Treatment of Cancer (EORTC) Heavy Particle Therapy Group. Full beam data are presented. The first study in the neutron therapy Program is on the treatment of squamous cancers of the head and neck. This consists of two parts. Part I is a dose searching phase and Part II is a comparison of our current photon treatment versus neutrons using the neutron dose selected by Part I of the study. Results of the dose searching phase (Part I) are presented.

Carcinoma, Squamous Cell

Total nodal radiation in progressive sarcoidosis. Case report.

The subject of this article is a patient with sarcoidosis with neurological involvement, who failed to respond to high dose steroid therapy and cyclophosphamide. Low doses (20 Gy) of total nodal and craniospinal irradiation resulted in an excellent response, the patient being alive and in good health 3 years after irradiation without any further steroid therapy.

Adult

Expression and function of ras proto-oncogene proteins in human sperm cells.

The presence and role of c-ras proteins were investigated in mature human sperm cells. The v-H-ras monoclonal antibody (mAb) against the c-ras protein, p21, reacted specifically with the acrosomal region of methanol-fixed as well as unfixed-live capacitated and non-capacitated human sperm cell in the indirect immunofluorescence technique. The v-H-ras mAb predominantly recognized c-ras protein of 21 kDa on the Western blot of lithium diiodosalicylate (LIS)-solubilized human sperm preparation. The incubation of sperm cells with v-H-ras mAb affected the sperm cell function in the human sperm penetration assay. The antibody significantly reduced the acrosome reaction and release of acrosin activity from the sperm cells. There was no effect of the mAb on percentage motility, although the mAb significantly affected various motility characteristics such as linearity, amplitude of lateral head displacement (ALH) and beat frequency, the motility parameters involved in the hyperactivation phenomenon of sperm cells leading to capacitation and acrosome reaction. These results suggest that the c-ras or c-ras-like proteins are present in mature sperm cell and may have a role in capacitation and/or acrosome reaction of human sperm cell.

Acrosin

The effect of head and neck cancer treatment on whole salivary flow.

The effects of multimodality therapy for head and neck cancer on whole salivary flow were evaluated. Eighteen subjects with head and neck cancer were studied. Resting and stimulated whole salivary flow rates were recorded, pretreatment, after individual modality therapy, and posttreatment. Twenty-four subjects with no history of head and neck cancer matched for age, and sex distribution, served as controls. Primary site, stage, major salivary glands resected, radiation fields, and dose to major salivary glands are reported. The average salivary flow rates for 18 subjects following treatment was reduced 83% for resting and 86% for stimulated saliva from pretreatment levels. The null hypothesis that the overall resting and stimulated whole salivary flow rates are unaffected by treatment (surgery and radiation) of the head and neck cancer was rejected (P values at 0.05 level of significance). Stage and location of primary, total dose delivered to and volume of gland exposure are important factors when predicting xerostomia following multimodality therapy.

Adult

A preliminary report of combination chemotherapy with cisplatin and mitomycin-C followed by radical hysterectomy or radiation therapy in patients with locally advanced cervical cancer.

Neoadjuvant chemotherapy with cisplatin and mitomycin-C was used in the primary treatment of 17 patients with locally advanced cervical cancer (stages Ib-IIIb; tumor diameter greater than 5 cm) prior to definitive local treatment with radical hysterectomy or radiotherapy. Thirteen of the seventeen patients (76.5%) responded to initial chemotherapy, permitting a radical hysterectomy in ten patients. At histologic examination of the surgically resected primary tumor and lymph nodes, complete pathologic responses were found in 2 patients and partial pathologic responses in 8 patients. The median follow-up time is 14.5 months with a median survival for all patients of 52 weeks. All responders are alive. No therapy-related deaths, major complications, or delay in treatment occurred. Neoadjuvant chemotherapy with mitomycin-C and cisplatin is feasible and may be of benefit for patients with locally advanced cervical cancer.

Adult

High-dose-rate afterloading brachytherapy, external radiation therapy, and combination chemotherapy in poor-prognosis cancer of the cervix.

Fourteen patients with poor-prognosis cervical cancer were treated with concurrent chemotherapy (cisplatin and mitomycin-C), external radiation therapy (RT), and high-dose-rate (HDR) brachytherapy. Pelvic RT was delivered as (a) external-beam radiation (four-field box technique, 40.0 Gy), (b) brachytherapy using HDR 60Co or 192Ir (3.80 Gy/fraction, thrice weekly; total dose, 46.83 Gy) with intrauterine stent, and (c) parametrial boost using an AP field with custom-fabricated step wedges. Post-radical-hysterectomy patients received 50.40 Gy external RT and 3.23 Gy/day vaginal cylinder HDR at 1/2-cm depth (total dose, 16.15 Gy). Complete clinical and radiographic response was noted in all evaluable patients who are alive with no evidence of disease, 3 to 27 months after completion of therapy (median, 9 months). Toxicity consisted of grade 2 to 3 hematologic toxicity (4 patients) and nausea and vomiting in all, but grade 3 in only 2 patients. One patient had grade 2 diarrhea. The only major complication (small bowel obstruction) occurred in a patient with lupus vasculitis. This pilot study demonstrates the feasibility of this regimen in an outpatient setting with acceptable toxicity. More prolonged follow-up of our patients is required to determine its impact on long-term survival.

Antineoplastic Combined Chemotherapy Protocols

Eye metastasis from carcinoma of the breast: diagnosis, radiation treatment and results.

The experience at the Gershenson Radiation Oncology Center of 32 cases of metastases to the eye or orbit from breast cancer are presented with a review of the literature. The 32 patients were referred for radiation therapy in the period of 1980-1991. Eighteen patients had metastasis to the choroid, 2 patients had involvement of other parts of the eye (anterior chamber +/- choroid), and 11 patients had orbital metastasis. In one patient, the diffuse nature of the disease prevents subsite assignment. Ten of the patients with eye metastases also had brain or meningeal metastases (8 patients concurrent with eye metastases). Four of the 32 patients had bilateral choroidal metastases. A complete course of radiation therapy was delivered to 28 patients, one patient was not treated and 3 patients received only partial treatment because of general deterioration due to other widespread metastases from breast cancer. Of 21 evaluable patients, 15 had definite improvement. There was no progression of the eye metastases in the other 6 patients. The rest (7 patients) were lost to detailed follow-up of the response of the eye metastases. Four patients are still alive without any severe long-term side-effects. The diagnosis, treatment and outcome is presented with a review of the literature. The importance of emergency treatment for rapidly progressing lesions is stressed as well as the need for detailed treatment planning, careful delivery of daily treatments with a high degree of reproducibility and precision to prevent possible damage to sensitive normal structures.

Adult

Initial experience with a practical hyperfractionated accelerated radiotherapy regimen.

This paper presents early results of a trial of a three-fractions-per-day (TID) regimen that is more convenient to schedule than the Continuous Hyperfractionated Accelerated Radiotherapy (CHART) protocol currently being tested in Europe. The treatment schedule used in the CHART regimen has been modified from 36 fractions of 1.5 Gy TID in 12 days to 72 fractions of 1.1 Gy in 24 treatment days, with all fractions delivered during normal working hours. With no weekend treatments, the entire course of radiotherapy is completed in less than 5 weeks. The doses used were determined using the L-Q model, with correction for incomplete repair between fractions and for accelerated repopulation of cancer cells. Comparison with historical controls shows statistically significant improvements both in CR rates for the primary tumor and in acute toxicity, as measured by reduced treatment interruptions. L-Q model calculations predict that, compared to the highest dose achieved in previous studies without exceeding tolerance, we are able to obtain a 12% increase in bioeffect dose to the primary tumor due to accelerating the treatment. An analysis of the potential tumoricidal effectiveness of this new treatment regimen shows that it should be better than several other accelerated fractionation schedules being tested for all values of Tpot. For short Tpot times, the advantage may be as much as one log cell kill, corresponding to a 10-15% potential improvement in local control.

Aged

Presence and role of c-myc proto-oncogene product in mammalian sperm cell function.

The presence and role of c-myc protein was investigated in mature sperm cells of the human, mouse, and rabbit. The monoclonal antibodies against c-myc protein (c-myc) reacted with the acrosomal region of the sperm of these mammalian species in the indirect immunofluorescence technique. The c-myc monoclonal antibody (MCA) recognized c-myc protein of 62 and 64 kDa on Western blots of lithium diiodosalicylate-solubilized sperm preparations of these species. The c-myc MCA showed a dose-dependent inhibition of human sperm penetration of zona-free hamster eggs, inhibition of murine in vitro fertilization, and reduced in vivo fertilization in rabbits. There was no effect of the antibody on percent sperm motility, though the antibody significantly affected various motility characteristics such as mean and maximum amplitude of lateral head displacement and curvilinear velocity involved in hyperactivation phenomenon of human sperm cells. These results suggest that c-myc or c-myc-like protein is present in mature sperm cells and may have a role in sperm cell function especially in capacitation and/or acrosome reaction.

Animals

Antibodies to sperm surface antigens and the c-myc proto-oncogene product inhibit early embryonic development in mice.

The effects of antibodies against sperm antigens and the c-myc proto-oncogene product on early embryonic development were investigated in mice. Affinity-purified Fab' antibodies against lithium diiodosalicylate (LIS)-solubilized murine sperm extract and fertilization antigen (FA-1) reduced (p less than 0.01 to p less than 0.001) blastulation rates of in vitro cultured 2-cell murine embryos primarily because of an arrest of development at the morula stage. Similarly, the c-myc monoclonal antibody (mAb) affected early embryonic development in a dose-dependent manner. These effects were specific, since immunoabsorption, with its respective peptide, completely blocked the inhibitory effect of the c-myc mAb. Anti-LIS sperm Fab' identified four protein bands (approx. 36, 29, 24.6, and 17.6 kDa) on Western blots of extracts from unfertilized and fertilized ova, one band (approx. 68 kDa) each on 4-8-cell embryo and morula extracts, and one band (approx. 53 kDa) on blastocyst extracts. Anti-FA-1 Fab' did not react with unfertilized or fertilized ova, but specifically identified two protein bands (approx. 53 and 25.7 kDa) on blots of 2-cell-embryo extract, one band (approx. 25.7 kDa) on morula extract, and one band (approx. 53 kDa) on blastocyst extract. The c-myc mAb did not react with any band corresponding to the c-myc protein on blots of extracts from unfertilized or fertilized ova, 2-cell embryos, 4-8-cell embryos, morulae, or blastocysts. These results suggest that some of the cross-reacting sperm antigens that are expressed during early cleavages, and the product of the c-myc proto-oncogene may have a role in normal early embryonic development.

Animals

Role of membrane phosphotyrosine proteins in human spermatozoal function.

The monoclonal anti-phosphotyrosine antibody (PTA) recognized proteins related to relative molecular mass regions of 94,000 +/- 3000 and 46,000 +/- 3000 Mr on Western blots of detergent-solubilized non-capacitated human sperm extract (HSE). The pattern of phosphorylation at tyrosine residues depended upon the physiological state of the sperm cells. At least six protein bands corresponding to four molecular regions of 94,000 +/- 3000, 46,000 +/- 3000, 25,000 +/- 7000 and 12,000 +/- 2000 Mr, respectively, were labeled with 32P when human sperm were capacitated in vitro; the proteins belonging to the former three regions were phosphotyrosine proteins as they were precipitable by PTA. In vitro kinase assay performed directly on HSE indicated autophosphorylation of proteins of the same four molecular regions, with the capacitated sperm preparations having 30% higher 32P incorporation into 94,000 +/- 3000 Mr proteins and 17% less incorporation into 12,000 +/- 2000 Mr proteins as compared to the non-capacitated sperm preparations. Both of these protein regions were also autophosphorylated at tyrosine residues when immunoprecipitated phosphotyrosine proteins were used for the kinase assay. Phosphorylation of tyrosine residues of 94,000 +/- 3000 Mr proteins was further stimulated by 1.38- to 1.46-fold in response to exposure to zona pellucida proteins, namely the porcine ZP3 and human zona proteins (HZP); the HZP induced the highest response. Immunofluorescence observations on fixed human sperm demonstrated that capacitation as well as exposure to zona proteins increased the degree of tyrosine-specific fluorescence per sperm cell as well as the number of sperm cells that showed fluorescence at the acrosomal region of the spermhead.(ABSTRACT TRUNCATED AT 250 WORDS)

Antigens

Results of treatment in locally advanced carcinoma of the endometrium.

The impact of treatment on survival was analyzed in 106 patients with carcinoma of the endometrium stage II (n = 61) and stage III (n = 45). There was no significant difference in survival in patients with stage II who were treated with radiation therapy alone or with combination of surgery and radiation therapy. Their five-year actuarial survival was 74.5% and 71.3% respectively (p = greater than 0.05). However, combined treatment was associated with significantly superior survival in patients with stage III disease where the survival was 57.3% versus 17.5% in patients who received irradiation alone (p = 0.01). Diagnosis of stage III disease based upon clinical (CS III) or pathological (PS III) findings was responsible for this difference in survival. Patients with CS III whose tumor could not be resected because of its extent carried poorer prognosis. Patients with stage II had excellent tumor control in pelvis as compared to patients with stage III. Treatment-related complications were minimal. Overall survival of patients with stage III was poor (33.8%) due to a high rate of pelvic and/or extrapelvic recurrences.

Adenocarcinoma

Assessment of the viability and fertilizing potential of cryopreserved bovine spermatozoa using dual fluorescent staining and two-flow cytometric systems.

A dual fluorescent staining system utilizing 5 (and-6)-carboxy-4',5'-dimethyl fluorescein diacetate (CDMFDA) and Hydroethidine (HED) was developed to provide quantifiable information reflective of spermatozoal viability and fertilizing potential. Cryopreserved spermatozoa from ten bulls on which there was fertilizing capacity information were incubated for 1.5, and 3 hr at 39 degrees C prior to fluorogenic staining. Spermatozoa were analyzed using both a FACS Analyzer and an EPICS V flow cytometer to determine if a particular fluorescence pattern was due to an instrumental artifact or cellular processes. Five fluorescent cellular populations were identified by the FACS Analyzer and three populations by the EPICS V. Spermatozoa were quantified after each incubation time for red (HED) and green (CDMFDA) fluorescence. Viable spermatozoa retained the greatest amount of both green and red fluorescence. Dead or moribund spermatozoa had a decrease in over-all fluorescence. The number of viable cells at 0 hr plus the number of dead or morbid cells at any time period were identified by the FACS Analyzer as important in estimating the potential fertility of a bull. The EPICS V identified the number of dead or moribund cells as being related to nonreturn rates. Incubation of samples decreased cellular viability, which resulted in reduced levels of both green and red fluorescence. Similarities between data obtained with both flow cytometers illustrated that cellular processes, not instrumental artifacts, were responsible for the decrease in over-all fluorescence when viability declined, the relationship between the number of cells with specific fluorescence levels and nonreturn rates, and the incubative-induced changes in fluorescence patterns.

Animals

Stage III carcinoma of the endometrium. Results of treatment.

The impact of treatment on survival was analysed in 45 patients with stage III carcinoma of the endometrium. Our results indicate that patients treated with a combination of surgery and radiation therapy did significantly better than those treated with radiation alone. The five-years survival was 57.3% and 17.5%, respectively (p = 0.01). Patients with clinical stage III (CS III) whose tumor could not be resected surgically did poorly than patients with pathological stage III (PS III). This difference, however, was not statistically significant (p = greater than 0.05). Treatment related complications were minimal. Overall survival of patients of 33.8% was directly attributable to increased pelvic and/or extra pelvic recurrences.

Adult

Combined modality therapy utilizing a cisplatin combination for effective chemotherapy in patients with previously untreated head and neck cancer.

In patients with locally advanced head and neck cancer, the results of standard definitive treatments of surgery, radiotherapy, or both were disappointing. The local and regional recurrence rates were high, despite adequate surgical resection with negative margins and postoperative radiotherapy to all known or possible disease areas. Combination cisplatin chemotherapy given initially before definitive treatments produced a high overall antitumor response and up to 50 percent clinical complete response. Before answering the question of value of chemotherapy as part of the multimodality treatment, it is important to identify the safest and most form of chemotherapy. The degre of chemotherapy effectiveness is defined by the incidence of clinical and, most important, histologic complete response. To assess this effectiveness, chemotherapy was given before definitive treatments to patients with measurable disease. From our 10 year experience we have concluded that continuing the development of induction chemotherapy, including investigating the timing of such effective treatment and assessing the value of such therapy, is of the utmost importance.

Antineoplastic Combined Chemotherapy Protocols

Study of food habits, food practices and taboos in Bangladesh: their implications in nutrition education.

The paper reports the findings of a retrospective study conducted to determine the prevailing food habits, food taboos and practices among 381 mothers selected randomly from twelve villages situated in 4 administrative divisions of Bangladesh. Undesirable food taboos and practices, maldistribution of food, lack of understanding of the nutritional needs of the vulnerable groups and bad cooking practices were found to be widespread in rural Bangladesh. Nutritional and health implications of these are discussed and remedial measures suggested.

Adult