Distribution and kinetics of CoEDTA in smooth muscle,and its use as an extracellular marker

1. [⁶⁰Co]EDTA has been evaluated as an extracellular marker in guinea-pig taenia coli and rabbit myometrium.2. The complex was found to be stable, non-toxic, convenient to use and had the advantage of being readily measured without interfering with the analysis of water and electrolyte contents.3. In both smooth muscles [⁶⁰Co]EDTA distributed rapidly into a volume equivalent to that available to [¹⁴C]sorbitol and slightly greater than that available to inulin.4. The optimum concentrations of carrier required to effectively saturate any adsorption sites were 0·1 mM-CoEDTA for taenia coli and 1·0 mM for myometrium.5. [⁶⁰Co]EDTA was distributed into a volume equivalent to the total water content of rabbit tendon, indicating that it was not excluded from connective tissue water.6. About 5% of the [⁶⁰Co]EDTA taken up by smooth muscle in 15 minutes exhibited slow efflux kinetics. This property was also exhibited by [¹⁴C]sorbitol and has been reported for other extracellular markers.7. The efflux of 95% of [⁶⁰Co]EDTA followed bulk diffusion kinetics for both taenia coli and myometrium.8. The simultaneous efflux of ²⁴Na indicated that 1-2% exchanged slowly while 98-99% of the ²⁴Na exchange could be described by bulk diffusion kinetics, similar to [⁶⁰Co]EDTA. About 15% of this ²⁴Na was contained outside of the [⁶⁰Co]EDTA space.9. More detailed studies involving the analysis of simultaneous efflux of [⁶⁰Co]EDTA and ²⁴Na may help to locate and characterize the properties of the excess rapidly exchanging sodium (12-15 m-equiv/kg. wet wt.) in smooth muscle.     

Vitamin B12--folate interrelations.

Megaloblastic anaemia is due to a derangement of DNA synthesis caused by insufficient supply of one or other of the four deoxyribonucleoside triphosphate (dNTP) precursors of DNA synthesis or by direct inhibition of one or other DNA polymerase. Reduced supply of the pyrimidine deoxythymidine triphosphate (dTTP) may be caused by folate or vitamin B12 deficiencies or by the action of dihydrofolate reductase inhibitors (e.g. methotrexate, pyrimethamine or trimethoprim), all of which cause reduced supply of the coenzyme 5, 10 methylene tetrahydrofolate (pentaglutamate) needed for thymidylate synthetase. Reduced dTTP supply may also be caused by direct inhibition of thymidylate synthetase by 5-fluorouracil. Reduced supply of both purines, deoxyadenosine triphosphate (dATP) and deoxyguanosine triphosphate (dGTP), may be caused by hydroxyurea, 6-mercaptopurine (and probably by another purine antagonist azaserine), whilst reduced supply of both pyrimidine DNA precursors, dTTP and dCTP (deoxycytidine triphosphate) may be due to inherited orotic aciduria or to treatment with azauridine. Cytosine arabinoside directly inhibits DNA polymerase. DNA replication is a discontinuous process and a number of enzymes are concerned with different aspects of the process. The parental strands partly unwind and a large number of initiation points or origins are activated on both strands. A primer RNA is first synthesised using the parental strand of DNA as template. Fragments of new DNA are then synthesised on the parental DNA template, starting at the RNA primer, under the action of one or other DNA polymerase (probably gamma). The RNA primer is then removed and the gap left is filled by further DNA synthesis under the action of a different DNA polymerase (probably alpha). The fragments of new DNA are joined to give newly synthesised stretches of DNA (replicons) which are then liigated together to form bulk DNA of enormous molecular weight. It is suggested here that reduced supply of one or other of the four deoxyribonucleoside triphosphate (dNTP) during the 'S' phase of the cell cycle (due to vitamin B12 or folate deficiency, drug treatment or other congenital or acquired abnormality in synthesis of the dNTP) impairs the cell's ability to elongate newly initiated DNA fragments by preventing gap-filling, the polymerase needed for gap-filling requiring substantially greater concentrations of the deoxyribonucleoside triphosphates than the polymerase involved in chain initiation. Cytosine arabinoside, which also may cause megaloblastosis, may affect principally the synthesis of new DNA fragments. Since active protein synthesis is needed for the cell to enter the S phase and RNA synthesis is needed to prime new DNA synthesis, megaloblastic anaemia may be expected to occur only when DNA synthesis is inhibited but protein and RNA synthesis are relatively unimpaired...     

GLUT1 expression in malignant tumors and its use as an immunodiagnostic marker

OBJECTIVE:

To analyze glucose transporter 1 expression patterns in malignant tumors of various cell types and evaluate their diagnostic value by immunohistochemistry.

INTRODUCTION:

Glucose is the major source of energy for cells, and glucose transporter 1 is the most common glucose transporter in humans. Glucose transporter 1 is aberrantly expressed in several tumor types. Studies have implicated glucose transporter 1 expression as a prognostic and diagnostic marker in tumors, primarily in conjunction with positron emission tomography scan data.

METHODS:

Immunohistochemistry for glucose transporter 1 was performed in tissue microarray slides, comprising 1955 samples of malignant neoplasm from different cell types.

RESULTS:

Sarcomas, lymphomas, melanomas and hepatoblastomas did not express glucose transporter 1. Forty-seven per cent of prostate adenocarcinomas were positive, as were 29% of thyroid, 10% of gastric and 5% of breast adenocarcinomas. Thirty-six per cent of squamous cell carcinomas of the head and neck were positive, as were 42% of uterine cervix squamous cell carcinomas. Glioblastomas and retinoblastomas showed membranous glucose transporter 1 staining in 18.6% and 9.4% of all cases, respectively. Squamous cell carcinomas displayed membranous expression, whereas adenocarcinomas showed cytoplasmic glucose transporter 1 expression.

CONCLUSION:

Glucose transporter 1 showed variable expression in various tumor types. Its absence in sarcomas, melanomas, hepatoblastomas and lymphomas suggests that other glucose transporters mediate the glycolytic pathway in these tumors. The data suggest that glucose transporter 1 is a valuable immunohistochemical marker that can be used to identify patients for evaluation by positron emission tomography scan. The function of cytoplasmic glucose transporter 1 in adenocarcinomas must be further examined.     

Vitamin B12 deficiency presenting as an acute confusional state: a case report and review of literature

Background

Vitamin B12 deficiency is associated with a wide spectrum of neuro-psychiatric manifestations.

Results

We report a case of a 44 year old female patient referred to the haematology unit with vitamin B12 deficiency presenting as an acute confusional state or delirium. Total resolution of the psychiatric symptoms occurred following parenteral vitamin B12 replacement therapy.

Conclusion

This case report highlights one of the neuro-psychiatric presentations of vitamin B12 deficiency in a previously healthy individual.     

Vitamin B-12b as an antidote for over-sedation

Several observations have led the author to conclude that massive injections of vitamin B-12b (hydroxocobalamin) will prove an excellent antidote for patients overdosed with sedatives/tranquilizers and/or alcohol.     

Counselling in an inner city general practice: analysis of its use and uptake.

BACKGROUND. In recognition of the emotional problems which frequently underlie somatic complaints, practices increasingly offer counselling as part of their services to patients. In an inner city practice, a combination of short term counselling, volunteer befriending, community outreach and social work services is offered as a means of responding to the full range of patients' counselling needs. AIM. This study set out to establish the use and uptake of these services. METHOD. A retrospective analysis of patients referred for counselling over one year was carried out. RESULTS. The analysis identified a broad range of emotional problems among referred patients as well as problems of a practical nature. A quarter of the patients referred failed to keep their initial appointments or to complete their contracts. One fifth of the patients were referred on for longer term counselling and/or psychotherapy. Subsequent feedback revealed that preparation of a patient before referral was an important factor affecting uptake of counselling. CONCLUSION. Early assessment of the use and uptake of such services is essential if they are to be integrated successfully and a counsellor's individual skills employed effectively.     

维生素B〈sub〉12〈/sub〉对抑郁症的辅助治疗

目的观察抑郁症患者血清维生素B12水平,探讨抗抑郁剂合并维生素B12治疗维生素B12缺乏抑郁症的疗效及安全性。方法对400名抑郁症患者进行血清维生素B12浓度测查,将筛查出的维生素B12缺乏的抑郁症患者70例,随机分为两组,各35例。对照组根据病情口服西酞普兰20～40 mg/次,每日1次,治疗8周;研究组根据病情口服西酞普兰20～40 mg/次,每日1次,同时合并使用维生素B12,治疗8周。研究组及对照组治疗前后1,2,4,8周末分别进行汉密尔顿抑郁量表（HAMD）评定;治疗后1,2,4,8周末分别评定副反应量表（TESS）;治疗前及治疗后4,8周末分别查血清维生素B12浓度。结果抑郁症患者血清维生素B12平均水平（359.7±183.2）pg/ml,维生素B12缺乏发生率为19.5%,研究组与对照组第1周末汉密尔顿抑郁量表评分差异无显著性（P＞0.05）,治疗第2,4、8周末有显著性差异（P〈0.01）,研究组有效率为94.3%,对照组为74.3%,两组差异有显著性（P〈0.01）,血清维生素B12浓度治疗后4,8周末有显著性差异（P〈0.01）,且研究组汉密尔顿抑郁量表评分与血清维生素B12浓度负相关。两组不良反应均较轻微,TESS评分比较差异无显著性（P＞0.05）。结论抑郁症患者血清维生素B12平均水平较正常明显降低,维生素B12缺乏发生率高,维生素B12辅助抗抑郁剂治疗可明显提高疗效,且不增加不良反应。     

Vitamin B12 absorption after allogeneic bone marrow transplantation.

The B12 absorption test (Schilling test) with intrinsic factor was used to examine ileal B12 absorption in 26 patients after allogeneic transplantation. The test was well tolerated and showed a profound fall in B12 absorption, which was maximal at two weeks after transplantation and recovered by eight weeks. The predominant influence on absorption at this stage was probably the conditioning schedule, and the presence of acute graft versus host disease (GVHD) was not associated with a further impairment of absorption. Six patients with chronic GVHD were studied. When compared with nine patients without GVHD there was a significant (p less than 0.005) reduction of B12 absorption. These findings suggest that the B12 absorption test may be a useful non-invasive method of studying bowel function after bone marrow transplantation.     

Galectin-3 expression in follicular tumours: an immunohistochemical study of its use as a marker of follicular carcinoma

AIMS: Galectin-3, a member of the beta-galactoside binding family of lectins, has been regarded as a useful tool for discriminating malignant tumours from benign nodules of the thyroid, including the distinction between follicular carcinoma and adenoma. However, there are follicular tumours with unclear vascular or capsular invasion, which makes diagnosis more difficult. In this study, we investigated the relationship between galectin-3 expression and the degree of vascular or capsular invasion of follicular tumours. METHODS: We immunohistochemically investigated galectin-3 expression in 260 cases of follicular tumour with various degrees of vascular or capsular invasion classified into four categories. RESULTS: The galectin-3 expression level significantly increased with the degree of vascular or capsular invasion (p<0.0001). However, its diagnostic value for follicular carcinoma was not high because the sensitivity and specificity were 68.7% and 57.5%, respectively. CONCLUSIONS: Our findings suggest that galectin-3 plays a role in the transformation of follicular tumours from benign to malignant; however, when diagnosing follicular tumours, the presence of this protein should not be required for diagnosing malignant transformation in all cases. Therefore, we must conclude that galectin-3 should only be considered an adjuvant marker for follicular carcinoma.     

Vimentin: an evaluation of its role as a tumour marker

In this study we examined 198 sarcomas, 38 carcinomas, 13 'tumours with a spindle cell component' and 22 malignant melanomas with a commercial monoclonal vimentin antibody. All histopathological material was formalin fixed and paraffin embedded. The results show this antibody to be a sensitive and specific marker of mesenchymal derivation or differentiation. It is a useful tool in separating sarcomas from most carcinomas, and in separating malignant melanomas from carcinomas. When used in combination with a cytokeratin antibody it identifies carcinosarcomas and synovial sarcomas.