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Biomedical subjects

T Halmos

Publications and source records attributed to T Halmos.

At least 19 recordsLinked to original sources

[Current interpretation of type 2 diabetes mellitus (NIDDM)].

The author introduces the classification of type 2. (NIDDM) diabetes. Special focus has to be directed to the slowly progressing type 1. (IDMM) form, which is masked behind the clinical picture of type 2. (NIDDM) diabetes. He points out the difficulties of differential-diagnosis among young diabetics. He draws attention on the growing importance of impaired glucose tolerance. Typical type 2 (NIDDM) diabetics seem to be members of a widened clinical entity, where hyperglycaemia is only one of the vascular and metabolic disorders. Basis of this multimetabolic syndrome lies on insulin resistance/hyperinsulinaemia. The syndrome seems to commence far before open diabetes can be diagnosed. A targeted screening for these patients might lead to a better infarct mortality rate in Hungary.

Adolescent

Production of highly specific monoclonal antibodies to monensin and development of a microELISA to detect this antibiotic.

Monensin, a polyether antibiotic of molecular weight 671 Da, was converted into a hemisuccinate and covalently linked to bovine serum albumin via the mixed anhydride method. Using this immunogen, polyclonal anti-monensin antibodies were raised in rabbits and monoclonal antibodies were prepared from mice. The specificity of the anti-monensin antibodies was examined by using several structural analogues as the immunogen and by performing direct binding and competitive microELISA assays on Terasaki plates. Rabbit polyclonal antibodies had a dissociation constant (KD) of 5.5 x 10(-8) M for monensin and reacted with nigericin, an antibiotic structurally related to monensin. In contrast, a mouse monoclonal antibody, 2H8, reacted only with monensin and had a much lower KD = 3 x 10(-8) M for monensin. Monoclonal antibody 2H8 was used to develop a competitive microELISA able to detect as little as 5 ng/ml of monensin in solution which corresponds to 75 pg or 110 fmol of this hapten per Terasaki well.

Animals

[Clinical picture of slow-evolving insulin-dependent diabetes mellitus]("1 1/2")].

The authors investigated the difficulties of differential diagnosis in diabetes, beginning in young age. They analysed the case records of fifteen young diabetics. The authors pointed out, that clinical diagnosis, carried out early, has utmost importance both of theoretical and practical significance, for correct classification according to the type of diabetes determines the therapy. In building the diagnosis, the clinician needs correct anamnestical, clinical data, immunogenetic markers (ICA, HLA), and the capacity of endogenous insulin secretion as well. In three patients they have observed a long period without insulin treatment that could be classified as remission phase. In eleven cases the treatment has started with oral antidiabetic drugs, one patient has got at he very beginning insulin treatment. At present, there is only one patient, still taking oral drugs. This diabetics has an ICA positivity in high titer, but he is refusing the recommended exogenous insulin treatment. In all of their cases the amount of injected daily insulin is low (0.3-0.6 IU/body weight/24 hours). Authors state by their careful analysis, that in all of their 15 diabetics there is existing a slowly developing type I IDDM, I/b, or very recently 1 1/2 diabetes form. The so called autoimmune form--described originally by Bottazzo--could have been disclosed in all of their cases.

Adolescent

[Hypertension and multimetabolic syndrome].

The occurrence of multi-metabolic syndrome was studied by authors on 31 patients with obesity of android type and hypertension. Plasma glucose and plasma insulin levels were investigated during oral glucose tolerance test, plasma lipid levels were determined, furthermore body mass index and waist/hip ratio were calculated. It was considered that in 65 percent of the cases the presence of multi-metabolic syndrome could have been proved. Dyslipidemia in 22 cases, hyperinsulinemia in 20 cases, deterioration of the carbohydrate metabolism in 14 cases could be demonstrated. The negative correlation between glucose- and insulin-responses to glucose challenge may suggest the presence of insulin resistance. No significant difference was found in metabolic parameters between men and women. The multi-metabolic syndrome is regarded by authors as a process which may lead to both type 2 diabetes mellitus and atherosclerosis. According to their appearance about two third of these patients could be screened. Authors emphasize the great significance of this problem and the importance of early diagnosis and prevention.

Adult

Plasma lipoprotein (a) concentration and phenotypes in diabetes mellitus.

Patients with Type 1 (insulin-dependent) and Type 2 (non-insulin-dependent) diabetes mellitus are at increased risk of developing atherosclerotic vascular diseases. A variety of lipoprotein abnormalities have been described as being associated with this increased risk. In this study, apo(a) isoform frequencies and lipoprotein(a) [Lp(a)] concentrations were determined in Type 1 and Type 2 diabetic patients in order to investigate a possible contribution of Lp(a) to the increased risk for atherosclerosis in diabetes. No significant differences in plasma Lp(a) concentrations were found in two ethnically different populations (Austrians from the province of Tyrol and Hungarians from Budapest) in either type of diabetes when compared to respective control groups (91 Type 1 and 112 Type 2 diabetic patients vs 202 control subjects in the Hungarian study and 44 Type 1 diabetic and 44 Type 2 diabetic vs 125 control subjects in the Austrian study). There were also no significant apo(a) isoform frequency differences between both patient groups and control subjects in the two study groups. These data, obtained from two large ethnically different populations, provide no evidence of a contribution of Lp(a) to the increased risk for atherosclerosis in diabetes.

Adult

[Doege-Potter syndrome. Fibrous mesothelioma of multicentric localization, causing hypoglycemia].

The authors present a case of a 73 year old female patient. She had a left side pleural mesothelioma and had been operated thrice. At the third operation an abdominal propagation joined to the thoracic mesothelioma. Starting from this third surgery severe hypoglycemic episodes illustrated the clinical pictures. The electronmicroscopy of the resected tumor mass documented the presence of neurosecretory granules. This strongly suggests that tumor mass produced a substance which could have been responsible for the hypoglycemic episodes. Due to the fact the insulin levels measured during severe hypoglycemias were always on a low level, we suppose that an insulin like material (IGF--II) was responsible for the above mentioned symptoms. The authors briefly review the literature.

Aged

Fatty acid conjugates of 2'-deoxy-5-fluorouridine as prodrugs for the selective delivery of 5-fluorouracil to tumor cells.

We have prepared a novel class of prodrugs by coupling 2'-deoxy-5-fluorouridine (5dFU) to oleic (18:1) and docosahexaenoic (22:6) acids, respectively. The cytotoxic activity of the drug and its conjugates (5dFU-18:1 and 5dFU-22:6) has been assayed in vitro upon HT-29, a colon carcinoma cell line of human origin. After short term (2-hr) treatments with the drugs, both fatty acid conjugates of 5dFU showed cytotoxic activity in a dose-dependent way, while 5dFU alone was devoid of toxic effects within the whole range of concentrations (10-200 microM) tested. Following long term (24- or 48-hr) incubations only a fraction of the HT-29 cell population was sensitive to 5dFU, the rest of the population being resistant even at the highest concentration tested (200 microM). In contrast, 5dFU-oleic acid and, particularly, 5dFU-docosahexaenoic acids appeared toxic for the whole population of HT-29 cells under the same experimental conditions. The considerable gain in cell toxicity and, to a lesser extent, in selectivity resulted from the conjugation since the toxic effect of the drug alone was not modified when equimolar mixtures of 5dFU and fatty acids were assayed. These results confirm a previous study on the cytotoxicity of fatty acid derivatives of chlorambucil toward malignant lymphoblastoid cells and reinforce the potential use of fatty acid conjugates as efficient anti-tumor prodrugs.

Cell Survival

[Is it permissible to treat young diabetics with oral antidiabetics?].

Authors analyzed the case history of 25 young diabetic patients, whose disease has been diagnosed before the age of thirty. The question that has been raised: is it allowed to treat young diabetics with oral drugs? By classifying the patients, they stated followings: In the 1. group they classified 16 verified MODY/NIDDY patients. In the second group they classified 3 young diabetics, whose disease had been evaluated as slowly progressing IDDM (autoimmune form). 3 patients belonged to the 3 group. They had been classified as MODY/NIDDY patients, however an extremely long lasting remission period--due to the short observation time--can not be excluded. The remaining 3 diabetic patients belonged to the IDDM group, with a long remission period. They were treated incorrectly with oral hypoglycemic drugs. Young diabetics can be treated with oral drugs only in case, when they are proven MODY/NIDDY patients. The precise differential diagnosis between this form and autoimmune IDDM, as well as long lasting remission periode, is extremely important.

Administration, Oral

Cytotoxicity of chlorambucil and chlorambucil-fatty acid conjugates against human lymphomas and normal human peripheral blood lymphocytes.

The cytotoxic activity of chlorambucil (Chl) and of chlorambucil-fatty acid conjugates of different degree of unsaturation have been assayed in vitro upon two human lymphoma cell lines and comparatively, upon quiescent and mitogen-activated lymphocytes from healthy blood donors. The cell toxicity observed with Chl-arachidonic acid and Chl-docosahexaenoic acid against lymphoma cells was, at any experimental condition used, equal or higher than the individual toxic potential of either chlorambucil or fatty acids. The two conjugates, like chlorambucil alone, were toxic against mitogen-activated lymphocytes. Contrary to chlorambucil, Chl-arachidonic at any concentration tested, lacked of toxicity towards normal non-activated lymphocytes. Chl-oleic acid conjugate was, whatever the cell species tested, much less toxic than Chl alone. In conclusion, the coupling of chlorambucil with polyunsaturated fatty acids increases: (a) the selectivity against neoplastic versus quiescent lymphocytes and (b) the toxicity for B-lymphoma cells. The selective effect of Chl-fatty acid conjugates is discussed in relation with the expression of an AFP/AFP-receptor autocrine system in malignant lymphoblastoid cells and in mitogen-activated lymphocytes.

Arachidonic Acids

[Long-term remission in diabetes mellitus diagnosed at an early age].

The authors deal with the clinical picture of total remission in diabetes, among young patients (below 30 years). In their interpretation "complete remission" means total withdrawal of insulin treatment for at least 2 months. Out of 14 patients with complete remission, the classified 7 patients--by clinical and immunogenetical parameters--as noninsulin-dependent diabetes in the young (MODY-NIDDY). 1 diabetic patient belongs to the autoimmune-subgroup of IDDM. The remaining 6 patients could be classified as IDDM-s. However their clinical and immunogenetical parameters were rather atypical. In conclusion they raised the possibility that this subgroup is heterogenous with in IDDM.

Adolescent

[Is diabetes mellitus, diagnosed between the ages of 30-45, a special sub-type?].

Diabetes diagnosed in the so-called middle age of life is debated from the typological point of view. The authors investigated 45 diabetics, whose disease had been diagnosed between the age of 30-45 years. As a result of their observations they state that diabetes in this age range is heterogenous. Patients can be classified into insulin-dependent and non-insulin-dependent types of diabetes. Two of their patients could be classified into a newly described subtype (early onset diabetes, EOD). For the time being it seems that the exact delineation of this new diabetic subtype needs more detailed observations.

Adult

The synthesis of branched-chain 3'-C-cyanomethyl-2',3'-dideoxy sugar nucleosides of adenine as potential inhibitors of the human immunodeficiency virus.

Condensation of the 3'-ketonucleoside 4 with diethyl cyanomethylphosphonate by a Wittig reaction afforded, after reduction of the unsaturated branched chain sugar nucleoside 5 with sodium borohydride, a mixture of 9-(2',5'-di-O-t-butyldimethylsilyl-3'-C-cyanomethyl-3'-deoxy-beta-D-ribo - and xylofuranosyl) adenines 6 and 7, which were separated after selective removal of the 5'-O-tBDMS group. Acetylation gave the monoacetylated ribo- and the triacetylated xylo compounds 10 and 11. Desilylation using tetrabutylammonium fluoride afforded the partially protected ribo isomer 12. The same treatment of 11 was accompanied by a N----O transacetylation giving the fully protected xylo compound 13a, from which the 2'-O-acetyl group was selectively removed using hydroxylaminium acetate. Treatment of 12 and 13b with phenoxythiocarbonyl chloride followed by deoxygenation with tributyltin hydride in the presence of azobisisobutyronitrile, and deacetylation in methanol saturated with ammonia afforded 9-(3'-C-cyanomethyl-2',3'-dideoxy-beta-D-erythro-pentofuranosyl) adenine 2 and 9-(3'-C-cyanomethyl-2'3'-dideoxy-beta-D-threo-pentofuranosyl) adenine 3.

Adenine

Alteration of insulin-binding receptors in non-insulin dependent diabetes of the young.

The behaviour of insulin binding receptors is rather unelucidated in non-insulin-dependent diabetes mellitus of the young. Authors in continuing their previous work studied the behaviour of insulin binding receptors of erythrocytes and monocytes in 9 MODY patients. They observed that specific insulin binding of circulating blood cells was significantly decreased in all cases as compared to the controls despite of a good state of metabolism (in the case of erythrocytes 4.63 +/- 1.1% vs. 6.03 +/- 1.7%, p less than 0.05, in the case of monocytes 2.3 +/- 1.2% vs. 3.6 +/- 1.4%, p less than 0.05). The lower value of insulin binding resulted from the decrease of receptor concentrations (in the case of erythrocytes 2.36 +/- 0.78 pmol/l vs. 3.81 +/- 1.14 pmol/l, p less than 0.05).

Adult

Growth hormone reserve in diabetes mellitus.

The magnitude of hGH reserve was investigated in young (16-40 years old) diabetic patients. Forty patients were examined with the arginine infusion test, twenty three with a sensitized version of the L-Dopa test. The patients were divided into four groups based on the type of their illness (IDDM or NIDDY) and the clinical stage of IDDM. It was concluded that the hGH reserve of the various diabetic groups differs from the hGH reserve of healthy persons as well as from one another. Taking into consideration the possible causes of these differences, it is suggested that the hGH reserve depends primarily on the metabolic condition of the patients, while the type of diabetes (IDDM or NIDDY) and the insulin therapy used may also be important contributing factors. Achievement of a good metabolic control within the same type of diabetes leads to the normalization of the previously pathologic hGH reserve.

Adolescent