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Biomedical subjects

A Martin

Publications and source records attributed to A Martin.

At least 469 records · Page 26Linked to original sources
PubMed1994

Preservation of functioning human thyroid "organoids" in the severe combined immunodeficient mouse. III. Thyrotropin independence of thyroid follicle formation.

The severe combined immunodeficient (scid) mouse allows the in vivo reconstitution of thyroid follicles from thyroid monolayer cells when transplanted sc within an extracellular basement membrane matrix. After 2-3 weeks, these human thyroid organoids show an active microfollicular histology and secrete human thyroglobulin into the murine serum in response to the administration of recombinant human TSH. Furthermore, such organoids survive for more than 3 months in this functional state. To assess whether thyroid follicular reconstitution was TSH dependent, we examined organoid follicular reconstruction in T3-induced hyperthyroid scid mice, in which endogenous murine TSH was presumed to be totally suppressed. By providing water with 12 micrograms/ml T3, we increased the murine serum T3 levels from a mean of 1.9 nmol/liter in controls to greater than 12.0 nmol/liter. After 3 weeks, thyroid cells derived from normal human thyroid monolayers were suspended in an extracellular basement membrane matrix, and the suspension was transplanted sc into scid mice (with or without T3-induced hyperthyroidism) and allowed to reconstitute. Histological examination 4 weeks later showed a similar degree of thyroid follicle formation in mice treated with or without T3, indicating that the hyperthyroid state had caused no interference with thyroid follicle reconstitution. This was further confirmed by transmission electron microscopy, which demonstrated normal human thyroid follicle cell polarity in the organoids of both euthyroid and hyperthyroid mice. In addition, using an extracellular basement membrane preparation with reduced growth factor (epidermal growth factor, insulin-like growth factor-I, and platelet-derived growth factor) levels also allowed normal thyroid follicle formation in T3-fed mice. These data demonstrate that in vivo thyroid follicle formation is TSH independent and that extrathyroidal epidermal growth factor, insulin-like growth factor-I, and platelet-derived growth factor may be relatively unimportant. The factors and molecular mechanisms leading to follicular reorganization of adult human thyroid cells remain to be determined, but are likely to depend largely on intrathyroidal growth factor secretion and cell-cell interaction.

Animals↗
PubMed1994

Engraftment of human lymphocytes and thyroid tissue into scid and rag2-deficient mice: absent progression of lymphocytic infiltration.

To study human autoimmune thyroid disease in an animal model we have investigated the in vivo survival of human thyroid tissues and functionality of human lymphocytes in severe combined immunodeficient (scid) mice and recombination-activating gene (rag2) knockout mice. We found successful engraftment of human thyroid tissues in both scid and rag2-deficient mice. However, when peripheral blood mononuclear cells were transplanted ip, human immunoglobulin production was poor in rag2-deficient mice compared to that in scid mice (mean human immunoglobulin G levels at 6 weeks, 0.2 +/- 0.2 microgram/mL in two of eight rag2-deficient mice compared to 20.8 +/- 7.0 micrograms/mL in seven of nine scid mice; P < 0.05). We, therefore, only pursued the further use of scid mice and transplanted them with thyroid tissue from patients with either Graves' disease (four patients) or Hashimoto's thyroiditis (one patient). At the functional level, we observed transiently increased thyroid hormone levels (T4 peaking at 5.4 +/- 0.2 microgram/dL compared to a normal level of 2.6 +/- 0.2 microgram/dL); human autoantibodies to human thyroglobulin, human thyroid peroxidase, and the human TSH receptor were also detected in thyroid-transplanted mice. In contrast to recent reports, histological examination of the thyroid explants showed no increase in the lymphocytic infiltrate compared to the original donor tissue, nor was there any thyroid follicular destruction observed. In fact, many of the transplants demonstrated a marked diminution in the infiltrates over time, with an absence of HLA-DR antigen expression by both T-cells and thyrocytes. Cotransplanted allogeneic thyroid tissues were unremarkable in terms of lymphocytic infiltrates and showed intact morphology. Taken together, these data point to a relative degree of T-cell inactivity within the thyroid explants from the scid mouse. Hence, a factor(s) present in the patient with autoimmune thyroid disease that activates their thyroid-specific T-cells may be absent in this murine model as presently constructed.

Animals↗
PubMed1994

Graves' disease thyroid tissue transplants in scid mice: persistent selectivity in hTcR Va gene family use.

We have analyzed the human T-cell receptor (hTcR) V alpha gene repertoire in thyroid tissue transplants of a patient with hyperthyroid Graves' disease. Blocks of thyroid tissue were transplanted subcutaneously into 10 mice with severe immunodeficiency (scid) and 4 weeks later 5 of the mice were injected intraperitoneally with autologous peripheral blood mononuclear cells (PBMC) (10(7) cells per mouse). After a further 3 weeks, mice were sacrificed and total cellular RNA and cDNA prepared from each of the explants. We used specific olingonucleotides in polymerase chain reactions (PCR) to amplify 18 different human hTcR V alpha gene families and the identity of the PCR fragments was confirmed by Southern blot analysis. Different samples of the donor thyroid tissue consistently expressed 9-10 of the 18 hTcR V alpha gene families screened (V alpha 1-7, 11, 12 & 15). A more marked bias in hTcR V gene family use was seen in each of the explants with a mean of only 2.8 V alpha gene families detected. After 7 weeks of transplantation, the thyroid explants largely reflected some of the same genes seen in the hTcR V gene repertoire of the donor tissue with particularly pronounced expression of V alpha 2 and V alpha 3 gene families. The transplantation of PBMC into the scid mice showed evidence for their accumulation within the transplanted thyroid tissues as judged by the appearance of additional hTcR V gene families expressed in these samples although the specificity of such accumulation remains unclear.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1994

Spinalis capitis, or an accessory paraspinous muscle?

A unilateral muscle, the location and dimensions of which do not exactly conform to existing descriptions, was found during dissection of the suboccipital region. The muscle in question extended from the spine and transverse process of the 6th cervical vertebra to the base of the skull. At its rostral attachment it blended with the insertion of the left rectus capitis posterior minor muscle on the inferior nuchal line. The caudal attachment arched over the semispinalis cervicis, separated from that muscle by an extensive venous complex. Medially, along the length of the muscle, weak fascial attachments to the ligamentum nuchae were present. Arterial branches from the occipital artery entered the muscle near its rostral end and nerve fibres and vascular channels from the lower cervical region entered the deep surface of the muscle.

Aged↗
PubMed1994

[Modelling of viscosity equivalent factor in the human muscle during muscular shortening].

The aim of this study was to calculate the theoretical variation of the non linear damping factor (B) as a function of the muscle shortening velocity. The theoretical variation of the B factor was determined from a muscle model which consists of a contractile component in parallel with a viscous damper both in series with an elastic component, and by using the characteristic equation of the force-velocity curve. In this muscle model, the viscous element modeled the inability of the muscle to generate as a big contracting force (while shortening) as possible under isometric conditions. The results show that the theoretical behaviour of the B factor was dependent on the shortening velocity and on the af parameter which varies according to the muscle fibre type composition and affects the curvature of the force-velocity curve.

Humans↗
PubMed1994

Digoxin amplifies the effects of deoxycorticosterone acetate (DOCA) in intact water-drinking rats: implications for the mechanism of DOCA hypertension?

INTRODUCTION: An increase in digitalis-like substances has been reported in deoxycorticosterone acetate (DOCA)-salt hypertensive rats. We hypothesized that the role of saline and unilateral nephrectomy in DOCA hypertension may be due to stimulation of endogenous digitalis-like substances. METHODS: We investigated the effects of digoxin and DOCA alone and in combination in intact rats drinking water. Forty male Sprague-Dawley rats were used (body weight 223-298 g). RESULTS: Neither digoxin (40 micrograms/kg per day, by gavage, for 35 days, n = 10) nor DOCA (30 mg/kg twice a week, subcutaneously, for 5 weeks, n = 10) caused a consistent increase in blood pressure in intact rats drinking water. In contrast, combined digoxin and DOCA administration (n = 10) increased systolic blood pressure from day 18 of treatment onwards, to a maximum at day 34 compared with sham-treated rats (n = 10). There were no consistent changes in water intake, urine volume, urinary sodium or potassium excretion, or plasma sodium or potassium concentration with digoxin treatment. DOCA increased water intake and urine volume, and caused an initial decrease in urinary sodium excretion, but no change in urinary potassium excretion or plasma sodium concentration. Plasma potassium excretion was lower in DOCA- than sham-treated rats. CONCLUSION: Combined digoxin and DOCA administration in intact rats drinking water increased blood pressure significantly compared with either drug alone, raising the possibility that the mechanism by which nephrectomy and salt loading contribute to DOCA hypertension in the rat might be through stimulation of endogenous digitalis-like substances.

Animals↗
PubMed1994

Comparative effects of dietary corn, fish and Krill oils on intestinal glycosylation.

Antarctic Krill is considered as a valuable protein resource for animal and human nutrition. Due to the high content of long chain polyunsaturated fatty acids of the n-3 family, Krill consumption could be also interesting in cardiovascular diseases. In the search for the demonstration of the absence of toxicity of Krill, we studied the effect of Krill oil, as compared to fish and corn oil, on the rat intestinal fucosylation process at weaning, a very sensitive model of the influence of nutritional factors. Krill oil containing diets were very well tolerated as compared to other currently used oils and induced only slight modification in fucose and mannose proportions in intestinal glycoprotein sugars. These modifications were not reflected in the enzymatic activities involved in the fucosylation pathway. These results confirm the harmlessness of Krill derived products and their possible use in human nutrition.

Animals↗
PubMed1994

[The determination of polyamines in tumors of the maxillofacial area].

Putrescine, spermidine and spermine are polyamines deriving from ornithine. These are vital molecules for cell duplication processes; in fact, enzyme inhibitors responsible for synthesis are able to block cell multiplication. It is interesting to observe that there is an increased concentration of the polyamines and enzymes responsible for synthesis in solid tumours in man and in biological fluids in subjects carrying tumours. The authors assayed the polyamine concentration in tumour tissue taken from 10 cases of parotid carcinoma, noting a considerable increase in their levels compared to healthy control tissues. The hypothesis of being able to use the level of polyamines present in biological fluids in order to make an early diagnosis of tumours has now been definitively abandoned, both due to the scarce specificity and sensitivity of the available methods and due to the fact that increased polyamine concentrations were also found in physiological conditions and in the presence of non-tumour diseases; however, it is now being examined whether it would be possible to use polyamine levels to assess the degree of biochemical tumour malignancy or to evaluate the response to surgical or pharmacological treatment in patients with malignant tumours.

Carcinoma↗
PubMed1994

In vitro modulation of interleukin-1 beta secretion by cultured rat doxorubicin-stimulated whole glomeruli and dissociated mesangial glomerular cells.

Doxorubicin-stimulated whole rat glomeruli and dissociated mesangial and resident glomerular macrophage cells produced the release of interleukin (IL)-1 beta cytokine. This activity increased after the addition of lipopolysaccharide (LPS) or LPS plus indomethacin to the cultures. In the presence of WEB2086 [platelet-activating factor (PAF)-acether antagonist], this activity showed a drastic reduction, without modification after sodium furegrelate (thromboxane synthetase inhibitor) was added to the cultures. Our results also demonstrate that this IL-1 beta activity is mainly produced by glomerular-resident macrophage cells. These findings support the important role by both IL-1 beta and PAF-acether mediator factors, at the cellular level, in the rat model of doxorubicin-induced nephrosis.

Animals↗
PubMed1994

Measles vaccine failures: lack of sustained measles-specific immunoglobulin G responses in revaccinated adolescents and young adults.

The measles-specific antibody responses of seronegative adolescents and young adults were evaluated after revaccination. Of 1650 previously vaccinated healthy volunteers between the ages of 10 and 30 years, 4.4% were found to be seronegative for measles antibodies and 9.9% had equivocal titers. Seronegative volunteers were revaccinated to measles and followed serially for development of measles-specific IgG. Of 43 subjects followed for at least 1 year, only 58% developed and maintained positive antibody titers; 12% never developed positive titers and 30% initially developed titers that fell below positive levels within 1 year. The peak titers achieved by those subjects who responded transiently were lower than those achieved by subjects who developed sustained responses. Thus even after the recommended two dose schedule of the current measles vaccine, some adolescents and young adults lack protective titers of measles-specific antibody.

Adolescent↗
PubMed1994

Reversal of doxorubicin-impaired wound healing using triad compound.

Triad is composed of Na pyruvate, vitamin E, and unsaturated fatty acids. We found that Triad, administered orally or topically, reverses wound healing that is impaired by doxorubicin (Doxo) in rats. Rats given Doxo (6 mg/kg i.v.) were wounded with linear dermal incisions, and the wound-breaking strength (WBS) was compared among groups of rats differently treated with Triad. Five groups of five rats each were studied. Triad was given orally using a 20 per cent Triad/rat chow mixture and topically as a 50 per cent Triad/petroleum base salve administered daily. All groups were wounded at postoperative day 0, at which time Doxo was given to groups II-IV. Group IV was fed oral Triad 7 days prior to wounding and until POD 21. All wounds were harvested at POD 21, and the mean WBS of each group was obtained using an Instron Tensiometer. Doxorubicin impaired normal wound healing by 40 per cent. Oral Triad restored WBS in Doxo-treated rats to 88 per cent of control values; topical Triad restored WBS to 80 per cent of control values. Moreover, treatment with topical Triad and oral Triad increased the WBS by 30 per cent and 50 per cent when compared with Doxo-only-treated animals. In conclusion, Triad has been shown to restore wound healing to nearly normal levels in doxorubicin-impaired wounds.

Acrylic Resins↗
PubMed1994

Bcl-2 expression in normal endometrium during the menstrual cycle.

Bcl-2 is a proto-oncogene initially described in the (14;18) translocation in follicular lymphoma. It has been shown to prolong cell survival by preventing apoptosis. Endometrium undergoes rapid proliferation and differentiation under hormone control and is thus an excellent model to study the hormone dependency of Bcl-2 expression. We studied Bcl-2 expression by an immunohistochemical method in 53 samples of normal endometrium randomly distributed throughout the menstrual cycle, as well as five samples of hyperplastic endometrium. Bcl-2 staining predominated in glandular cells and peaked at the end of the follicular phase. Bcl-2 expression disappeared at the onset of secretory activity. The stroma, surface lining epithelium and arterial vessels also displayed cyclic variations in Bcl-2 expression. These results strongly suggest hormone-dependent regulation of Bcl-2 expression, which could play an important role in tumorigenesis.

Adult↗
PubMed1993

Decreased activities of phosphatidate phosphohydrolase and phospholipase D in ras and tyrosine kinase (fps) transformed fibroblasts.

The activity of N-ethylmaleimide-insensitive phosphatidate phosphohydrolase (PAP-2) was characterized in control, ras-transformed, and tyrosine kinase-(fps) transformed rat fibroblasts. PAP-2 was assayed in two different ways: 1) within its natural membrane using liposomes of phosphatidate and 2) in the presence of sufficient Triton X-100 to solubilize PAP-2, and to form mixed micelles with the phosphatidate. Harvesting the fibroblasts in medium containing orthovanadate and Zn2+ gave up to 3-fold higher PAP-2 activities when measured in the absence, but not in the presence, of Triton X-100. PAP-2-specific activities from both assays increased in the control fibroblasts as the cells reached confluence. Both specific activities were lower in the oncogenically transformed fibroblasts than in controls at all cell densities tested. The specific activities of PAP-2 did not increase with time in culture in transformed cells which continued to divide. The relative increase in activity of phospholipase D after stimulation with serum or phorbol myristate acetate was lower in the transformed fibroblasts compared to control cells. This indicates a coordinated decrease in the phospholipase D/phosphatidate phosphohydrolase pathway at the level of both enzymes in ras and fps transformed fibroblasts. The ratio of the production of diacylglycerol relative to phosphatidate, after stimulation with serum, or phorbol ester, was lower in both transformed fibroblasts relative to the controls. This is compatible with the decreased specific activity of PAP-2 and indicates functional significance for the differences in PAP-2 activity in regulating the balance between the two mitogenic lipids, phosphatidate and diacylglycerol. Control of PAP-2 activity could be an important factor in regulating appropriate signals for cell division.

Animals↗
PubMed1993

Amino acids of the recombinant kringle 1 domain of human plasminogen that stabilize its interaction with omega-amino acids.

A series of strategically designed recombinant (r) mutants of the kringle 1 region of human plasminogen ([K1HPg]) have been constructed and the resulting gene products employed to reveal the identities of the residues that contribute to stabilization of the binding of omega-amino acid ligands to this domain. On the basis of determinations of the binding constants of the ligands, 6-aminohexanoic acid and trans-4-(aminomethyl)cyclohexane-1-carboxylic acid, to a variety of these mutants, we find that the anionic site of the polypeptide responsible for stabilization of the amino group of the ligands consists of both D54 and D56 and the cationic site of the polypeptide that interacts with the carboxylate group of the ligand is composed solely of R70. The main hydrophobic interactions that stabilize binding of these ligands, likely by interactions with the ligand hydrophobic regions, are principally due to W61, Y63, and Y71. The results obtained are consistent with conclusions that could be made from analysis of the X-ray crystal structure of r-[K1HPg] and from previous studies from this laboratory regarding the binding of ligands of this type to the kringle 2 region of tissue-type plasminogen activator ([K2tPA]). It thus appears as though a common ligand binding site has evolved in different kringles with ligand specificity differences between r-[K2tPA] and r-[K1HPg] perhaps explainable by the different nature of the cationic sites on these polypeptides that are involved in coordination to the ligand carboxylate groups.

Amino Acid Sequence↗
PubMed1993

Transcriptional analyses of the gene region that encodes human histidyl-tRNA synthetase: identification of a novel bidirectional regulatory element.

A recombinant phage clone containing the 5' end of the gene HRS encoding human histidyl-tRNA synthetase (HRS) has been isolated. Primer extension analyses indicated that there are two types of HRS transcripts. The longer transcripts were initiated from a single transcription start point (tsp) located approximately 455 bp upstream and the shorter transcripts were initiated from multiple tsp located approximately 38 to 82 bp upstream from the HRS ATG start codon. Functionally, we have identified two regions (+1 to -122; -185 to -502), each of which when placed 5' of a promoterless cat construct can initiate transcription in both orientations after transfection into HeLa cells. A pair of imperfect inverted repeats (IIR) was located within the region +1 to -122. Using mobility shift assays, we have identified a nuclear factor that binds specifically to each half of the IIR. However, this pair of IIR (-73 to -110) was not sufficient for bidirectional transcription activity. At least one copy of a 27-bp oligodeoxyribonucleotide (oligo), which spans -94 to -120, was required in order to facilitate bidirectional transcription activity. From mobility shift assays using HeLa cell nuclear extracts and this 27-bp oligo, we have identified two DNA-protein complexes, both of which are presumably required to initiate bidirectional transcription.

Amino Acid Sequence↗