PubMed HealthSearch

Biomedical subjects

L J Valenta

Publications and source records attributed to L J Valenta.

At least 19 recordsLinked to original sources

Are all males equal? Anatomic and functional basis for sexual orientation in males.

In non-human primates anterior hypothalamic nuclei are closely involved in heterosexual activity in males. In humans, hypothalamic nuclei which correspond to these nuclei in non-human primates have been shown to have a neuronal density in homosexual men that is approximately half of that seen in heterosexual men. In addition, homosexual men exhibit a positive luteinizing hormone response to acutely administered estrogen that is intermediate between women (flat response) and heterosexual men (exaggerated response). Furthermore, on the basis of serum testosterone concentrations in similarly feminized transsexual males on estrogen/progestogen treatment 3 distinct groups can be identified. It is postulated that anatomic differences in the anterior hypothalamic nuclei that regulate sexual orientation in males may lead to alteration in the gonadotropin releasing hormone (GnRH) pulse/frequency leading to a more female-type pattern of gonadotropin secretion in homosexual males. Based on data in transsexual males this pattern may be more or less of the female-type in subsets of male homosexuals.

Animals

Hormone pattern in pharmacologically feminized male transsexuals in the California State prison system.

The hormonal profile of 40 transsexual inmates from a pool of 86 inmates in the California State prison system was studied before and after therapy with feminizing hormones. Clinical and social data were obtained on all 86 inmates; the incidence of human immunodeficiency virus (HIV) seropositivity was examined in 76 of the 86 individuals. Despite similar degrees of feminization in all 40 individuals in whom hormonal studies were performed, variable suppression of serum testosterone concentrations was present. Based on their testosterone concentrations while on feminizing hormone therapy, the transsexual inmates could be divided into three groups. In Group I (the "suppressed" group), the serum testosterone concentrations were markedly depressed (less than 10 ng/dL); in Group II (the "non-suppressed" group), the values of testosterone were normal (446 to 1072 ng/dL); and in Group III (the "intermediate" group), the testosterone values were between those of the suppressed group and the nonsuppressed group. We speculate that feminizing hormone therapy may induce the development of a state of target hormone resistance to testosterone that results in similar degrees of feminization independent of the circulating concentrations of testosterone. The incidence of HIV seropositivity (3/76) was considerably less than anticipated based on previous studies in populations at high risk for developing the acquired immunodeficiency syndrome.

Adult

Esophageal motor function in Graves' disease.

Esophageal motor function was studied in 10 patients with untreated Graves' disease and 15 healthy volunteers who served as controls. A noncompliant recording system with a triple-lumen assembly was used. Resting upper- and lower-esophageal-sphincter pressures, amplitude, duration, and velocity of peristaltic contractions in the body of the esophagus, and the number of repetitive and simultaneous contractions were measured. There was no significant difference in peristaltic amplitude and duration between the controls and the patients with Graves' disease. However, there was a significant increase in velocity of contractions in Graves' disease as compared with controls. On restudy of 5 patients who became euthyroid after treatment with 131I, all the measured parameters were unchanged except for velocity of the peristaltic contractions. The value for this measurement decreased essentially to the same as that found in the control subjects. It is concluded that: (1) thyrotoxicosis increases the propagation velocity of esophageal contraction, and (2) thyroid hormones may play a physiologic role in the control of esophageal motor function.

Adult

Thyroid function studies in the nephrotic syndrome.

Total serum and urinary thyroxine (T4), triiodothyronine (T3), and thyroxine-binding globulin (TBG) as well as serum free T4, thyroid-stimulating hormone (TSH), and T3 resin uptake (T3RU) were measured in seven patients with the nephrotic syndrome. The nephrotic syndrome was defined by proteinuria exceeding 3 g/24 h. All patients were clinically euthyroid. Most values for total serum T4, free T4, T3, T3RU, TBG, and TSH were within normal limits. However, the mean serum T3 and TBG values were significantly lower in patients compared with the control group. The values (mean +/- 2 SD) for urinary T4 were 24.3 +/- 20.3 in the patient group and 1.5 +/- 0.7 microgram/24 h in the control group. Urinary T3 values for patients and the control group were 2100 +/- 856 and 848 +/- 253 ng/24 h respectively. Urinary TBG was 2.1 +/- 1.8 mg/24 h in the patients and undetectable in the control group. There was no correlation between daily urinary T3 and T4 and urinary TBG. There was a weak correlation between daily urinary protein excretion and urinary T4 (r = 0.5).

Adult

Luteinizing hormone secretion and gonadotropin releasing hormone binding in heifer and steer anterior pituitaries.

Luteinizing hormone (LH) release and tissue content were studied in explanted bovine pituitaries from heifer and steer during superfusion in vitro. Compared to steer, heifer pituitaries contained significantly more LH and released more LH into the incubation medium. Quantitative response in LH release to gonadotropin releasing hormone (GnRH) stimulation was about equal in heifer and steer, but relative increase was more pronounced in steer. Specific 125I-GnRH binding to dispersed anterior pituitary (AP) cells and isolated plasma membranes was also analyzed. Concentration dependent binding curve of 125I-GnRH to dispersed cells exhibited sigmoid characteristics suggesting positive cooperativity. There was a sex dependent difference, the binding curve for heifer being shifted to the left and reaching saturation at lower GnRH concentrations than that for steer. "Multisigmoid" concentration dependent GnRH binding curves were obtained using isolated plasma membranes, revealing the presence of multiple binding sites. One of the binding sites, present in heifer, was absent in the steer derived materials, but could be induced by pretreatment of the steer plasma membranes with 17-beta estradiol as low as 50 pg/ml. It is concluded that the differences in GnRH binding may be responsible, at least in part, for the observed differences in LH secretion pattern between heifer and steer.

Animals

Binding of gonadotrophin releasing hormone (GnRH) by bovine anterior pituitary plasma membranes and purified GnRH receptor protein (GnRH.R).

[125I]-(GnRH) concentration dependence binding curves using isolated bovine anterior pituitary plasma membranes, intact and solubilized, and purified GnRH receptor protein, are compared. In all instances the concentration dependence binding curves had a stepwise character here interpreted as multisigmoid, with several steep increases and plateaus. These curves are compatible with the existence of several binding sites for GnRH. Purification of the GnRH receptor protein (GnRH.R) resulted in about 500 000-fold increase of binding activity and yielded a single protein species on polyacrylamide gel electrophoresis in SDS, of estimated molecular weight 60 000. Similarity of GnRH binding by the purified protein with that of intact and solubilized plasma membranes suggested that a single protein was responsible for the binding in each instance. Thus heterogeneity of GnRH binding is likely attributable to phase transitions of a single receptor protein into different allosteric forms. The data suggest that positive cooperativity is involved in the studied system.

Animals

Microfollicular thyroid carcinoma with amyloid rich stroma, resembling the medullary carcinoma of the thyroid (MCT).

A human thyroid tumor is described which, on light microscopy, exhibited the features of medullary carcinoma of the thyroid (MCT). The cells were arranged in solid lobules or trabeculae, and the stroma was abundant and gave positive reaction for amyloid as assessed by congo red, crystal violet and thioflavin T stains. However, there was microfollicular differentiation in certain portions of the tumor even where the tumor was invasively growing. On electron microscopy, numerous microfollicles were identified even where unsuspected by light microscopy. There were junctional complexes, the cells possessed well developed rough endoplasmic reticulum, prominent Golgi and numerous dense bodies obviously derived from the Golgi vesicles, which were of the same morphology as "secretory" granules described previously by some authors in MCT. However, we find this kind of cytology typically in microfollicular thyroid carcinomas. Presence of about 100 A thick fibrils in the stroma was consistent with histochemically positive amyloid. The biochemical data were compatible with the differentiated follicular cell origin of the tissue. The homogenate contained poorly iodinated thyroglobulin, and thyroid peroxidase activity. Calcitonin was undetectable by a sensitive radioimmunoassay. It is concluded that this tumor was follicular thyroid carcinoma with amyloid rich stroma. The presence of amyloid and dense bodies with homogenous electron dense contents is insufficient for making conclusions about histogenesis of thyroid tumors. The so called MCT with amyloid stroma probably represents a heterogenous group of thyroid tumors, at least some of them derived from follicular epithelium.

Adenocarcinoma

Ultrastructure and biochemistry of thyroid carcinoma.

Thirty-two thyroid tumors, 9 benign, 23 malignant, and 12 samples of normal thyroid tissue were examined by light and electron microscopy. Thyroglobulin content was also measured in the tissues and, in a limited number of cases, enzymatic activities were determined, such as thyroid peroxidase-iodinase, acid protease, and deiodinase. The presence of significant amounts of 19S, 27S and 12S thyroglobulin was well correlated with the ability of the tumors to accumulate radioiodine. It is suggested that the presence of thyroglobulin be used as a marker of potential function of thyroid carcinoma. Two types of ultrastructural changes were observed in thyroid carcinoma. The first one was interpreted as accompanying the progressive loss of function of thyroid tumors, and was represented by the modifications of highly specialized structures such as RER, lysosomal dense bodies, colloid, etc. The second one is suspected to reflect the malignant transformation of the follicular cell. This concerned namely the nuclei, mitochondria, and intracytoplasmic inclusions. These changes may have a diagnostic value since they were not observed in benign conditions.

Adenocarcinoma

Ovarian dysgenesis due to 45 X, 0/46 dic (X) mosaicism.

A 16 year old girl was evaluated for short stature, primary amenorrhea, and lack of development of secondary sex characterisics. She did not have the classical phenotypic signs of Turner's syndrome. However, she was short, had infantile genitalia and the adnexa were not palpable. There was a minor bone malformation and no signs of visceral abnormalities. The hormonal studies showed hypergonadotropic hypogonadism and borderline hypothyroidism. The rest of the endocrine functions was normal. The Barr bodies on the buccal smear were decreased and in part abnormal, large or bipartite. The karyotype showed mosaicism of about equal proportions of 45 X, 0/46, X, dic (X). The large dicentric chromosome was due to the end to end fusion of two X chromosomes by their short arms. Sequential binding studies were performed and failed to document any loss of genetic material of the dicentric X. It is speculated that the fusion of X chromosomes during an early mitotic division was responsible for the 45 X, U cell line, and that the short stature and gonadal dysgenesis in this patient was due to the presence of the 45 X, 0 line.

Adolescent

Iodopeptides from human thyroglobulin.

Human thyroglubulin labelled in vivo by 125I was purified from eight different thyroid glands including normal thyroid tissue, thyrotoxic goitre and euthyroid multinodular goitre. The purified protein was cleaved with cyanogen bromide (CNBr) and the resulting peptides were separated by column chromatography and ion exchange chromatography. Reproducible elution profiles of both protein and iodine were obtained. However, the distribution of iodine depended on the iodine content of the intact thyroglobulin. Small CNBr peptides seemed to be preferentially iodinated, but with a limited capacity. With higher degrees of iodination, larger peptides became richer in iodine. This suggests sequential iodination of the thyroglobulin molecule. The mixture of small peptides was digested by trypsin. Two iodopeptides were identified in this material by peptide mapping and they had identical migration in thyroglobulins of different origin. One of them was purified by ion exchange chromatography and high voltage electrophoresis. Analogous amino acid composition was obtained for the iodopeptide purified from two different thyroglobulins. The data indicates that thyroglobulin iodination occurs in specific portions of the polypeptide chain and probably in a sequential manner.

Amino Acid Sequence

Electron microscopy of clear cell thyroid carcinoma.

Three thyroid carcinomas composed in part or entirely of clear cells were studied by light and electron microscopy, and thyroglobulin content was determined by biochemical methods. Clear cells have been found in follicular and papillary thyroid carcinomas and in undifferentiated carcinomas. The clear (wasserhelle) appearance of the cytoplasm was due to the accumulation of glycogen. The major ultramicroscopic features of the clear cells were the presence of glycogen granules, the decreased amounts of rough endoplasmic reticulum, the increased amounts of free ribosomes arranged in polysomes, a hypertrophic Golgi apparatus, and a sparsity of dense bodies of lysosomal character. It is hypothesized that the intracellular accumulation of glycogen may be a result of a selective loss of the peptide portion of thyroglobulin, and may influence the degree of biochemical differentiation and the natural course of the tumors.

Adenocarcinoma

A syndrome of functional hypogonadotropic hypogonadism and sterility in a male with elevated serum estradiol.

A 36-year-old male complaining of impotence was examined. He was a genotypic male. Phenotypically, he exhibited signs of long-standing estrogen excess, such as feminine body build, gynecomastia, and varicose veins. His testes were soft and borderline small, and his prostate was small and soft. However, he had a normal-sized penis, normal male hair distribution, normal sense of smell, and normal intelligence. The laboratory data were compatible with mild hypogonadotropic hypogonadism. Serum estradiol (E2) levels were consistently elevated. The patient had azoospermia and a decreased semen volume. Inappropriately low levels of luteinizing hormone and follicle-stimulating hormone responded normally to gonadotropin-releasing hormone and clomiphene citrate. Levels of both testosterone (T) and E2 increased dramatically after prolonged clomiphene medication and in response to human chorionic gonadotropin. There was no change in either T or E2 levels in response to manipulations of the pituitary-adrenal axis. It is concluded that the elevated E2 level was responsible for suppression of gonadotropins which, in turn, caused mild hypogonadism and sterility in this patient. According to the stimulation tests, the source of the elevated E2 levels was testicular.

Adolescent

Thyroid peroxidase, thyroglobulin, cAMP and DNA in human thyroid.

Tissues from normal thyroid, euthyroid multinodular goiter, toxic goiter, Hashimoto's thyroiditis, thyroid adenoma, and carcinoma were examined for their content of deoxyribonucleic acid (DNA), thyroid peroxidase activity (TPA), thyroglobulin (TG), and adenosine 3',5'-cyclic monophosphate (cAMP). Compared with normal thyroids DNA was increased in the neoplastic tissues and decreased in euthyroid multinodular goiter. Quantitative changes of thyroglobulin were observed, especially in the thyroid tumors, and, in one case, immunoreactive 4S thyroglobulin-like protein was identified in the absence of 19S. TPA was grossly elevated in toxic goiter. This may be of significance in the pathogenesis of Graves' disease. TPA remained elevated even after adequate control of hyperthyroidism by preoperative PTU treatment. The cyclic AMP concentration in toxic goiter did not statistically differ from normal. This may indicate that extrathyroidal regulatory factors have a lesser role in the genesis and perpetuation of Graves' disease than otherwise believed. Cyclic AMP is known to exert a negative influence on tissue growth, and low concentrations in neoplasia have been reported. The values in the thyroid tumors studied were elevated, requiring further explanation.

Cyclic AMP