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R Lala

Publications and source records attributed to R Lala.

At least 37 records · Page 2Linked to original sources
PubMed1998

Isolation and structural and genetic analysis of the mouse enkephalin gene and its d(AC/TG)n repeats.

Enkephalins, the endogenous opioids, mediate a wide variety of intercellular communications through ontogeny and their involvement has been suggested in drug addiction and alcohol abuse as well as in various neuropsychiatric disorders. In order to generate a genetic model, we have isolated the mouse enkephalin (mENK) gene, analyzed its regulatory region and compared its structure to the well characterized rat ENK (rENK) gene. We analyzed 2600 bp and found 3 highly homologous regions: The highest level (98%) of positional and sequence homology between mice and rats was in the TATA/proximal regulatory region. This region contains all the inducible regulatory elements (enkCRE1, NF1, AP-2, NFkappaB, etc.) and also an octamer-like element at -543 bp. This high homology is interrupted in both mice and rats by the typically polymorphic d(AC/TG)n and d(TC/GA)n dinucleotide repeats positioned between nucleotides -670 and -950. The position and orientation of these repetitive elements differ substantially in the two species. Genomic PCR analysis of the d(AC/TG)n repeat in various mouse strains, including aberrant behavioral or neurological phenotypes, showed lack of polymorphism at this repeat. The positional and sequence homologies between the rat and the mouse ENK genes decrease in more upstream regions due to the presence of nonhomologues repetititve DNA sequences.

Animals↗
PubMed1998

Bone density and metabolism in thalassaemia.

Twenty-seven thalassaemic patients (13 F, 14 M, aged 8.1-14.9 yr), regularly transfused and chelated with desferrioxamine (30-40 mg/kg/day) were studied. Every patient was submitted to auxological evaluations, dual X-ray absorptiometry to measure bone mineral density (BMD), and to the determination of bone metabolic markers of osteoclastic activity (total urinary hydroxylysylpyridinoline crosslinks, carboxyterminal pyridinoline crosslinked telopeptide of type I collagen [ICTP]) and of osteoblastic activity (bone Gla protein [BGP] and carboxyterminal propeptide of type I procollagen [PIPC]). The evaluations were repeated after 1 year, during which 13 patients continued desferrioxamine chelation while 14 underwent deferiprone chelation (75 mg/kg/day in 3 doses). The data demonstrate widespread bone alterations consisting of osteoporosis, growth failure and bone age delay. Lumber spine (L2-L4) BMD areal values (Z score) inversely correlated with age, as did height SDS of both male and female patients, indicating osteoporosis progressing with age in parallel with growth insufficiency. No clear-cut alterations in bone mineral metabolism were found in basal state and after 1 year. Extensive MR imaging studies are needed to define the contribution of residual bone marrow hyperplasia to thalassaemic osteopathy suggested by subtle radiological signs as enlargement of bone marrow cavities with thinning of the cortical bone and abnormalities of the trabecules of spongy bone.

Absorptiometry, Photon↗
PubMed1997

Mutations in human TBX3 alter limb, apocrine and genital development in ulnar-mammary syndrome.

Ulnar-mammary syndrome is a rare pleiotropic disorder affecting limb, apocrine gland, tooth and genital development. We demonstrate that mutations in human TBX3, a member of the T-box gene family, cause ulnar-mammary syndrome in two families. Each mutation (a single nucleotide deletion and a splice-site mutation) is predicted to cause haploinsufficiency of TBX3, implying that critical levels of this transcription factor are required for morphogenesis of several organs. Limb abnormalities of ulnar-mammary syndrome involve posterior elements. Mutations in TBX5, a related and linked gene, cause anterior limb abnormalities in Holt-Oram syndrome. We suggest that during the evolution of TBX3 and TBX5 from a common ancestral gene, each has acquired specific yet complementary roles in patterning the mammalian upper limb.

Abnormalities, Multiple↗
PubMed1997

Long-term outcome of male-limited gonadotropin-independent precocious puberty.

Long-term outcome of five new cases of male-limited precocious puberty (MPP) is reported. Three patients had positive family history. One patient was untreated; 2 boys received cyproterone acetate (2.0-3.6 mg/kg/daily) without clinical effects. Two patients were treated with ketoconazole (600 mg/daily); in 1, GnRH analogue therapy (Buserelin, 1,600 microg/day) was added after 6 months of effective ketoconazole treatment for development of central precocious puberty. The other patient did not develop central puberty under ketoconazole treatment and improved his predicted adult height from 172.4 to 181.1 cm. Four patients reached final height [B.A. (therapy cyproterone acetate): age 22.0 years, -2.0 SDS; B.G. (untreated): age 15.5 years, -1.7 SDS; M.M. (therapy cyproterone acetate): age 19.5 years, -1.6 SDS; M.F. (therapy ketoconazole plus GnRH analogue): age 21.3 years, -2.2 SDS]; three had reduced testicular volume (B.A.: -1.6/-1.6 SDS; B.G.: -2.1/-2.1 SDS; M.F.: -2.4/-1.9 SDS); one (M.F.) showed oligospermia. We concluded that in MPP cyproterone acetate treatment did not improve final height; ketoconazole was effective in reducing testosterone secretion, but its real effect on final height cannot be determined; the timing of central puberty may be precocious, suggesting that an adjunctive GnRH analogue treatment may be needed. In some patients, testicular impairment may be present in young adulthood.

Androgen Antagonists↗
PubMed1997

Early hormonal and surgical treatment of cryptorchidism.

PURPOSE: We investigated the efficacy of early gonadotropin treatment of cryptorchidism for promoting testicular descent and ameliorating testicular histology. MATERIALS AND METHODS: We treated 319 cryptorchid testes in 281 boys 4 months to 3 years old with luteinizing hormone-releasing hormone and human chorionic gonadotropin sequential therapy. Surgery was done on the 207 testes that did not respond to medical treatment. Microscopic biopsies were performed in 134 of these 207 testes. Histological findings were compared to those of 30 cryptorchid testes in boys younger than 1 year who underwent surgery without previous hormonal treatment. RESULTS: Combined luteinizing hormone-releasing hormone and human chorionic gonadotropin treatment induced scrotal descent of a percentage of cryptorchid testes depending on clinical position. Therapeutic success was greater when testes were in a lower position and results were not age dependent. Hormonal treatment of cryptorchidism during the first year of life stimulated spermatogonia maturation. CONCLUSIONS: When administered at the end of age 6 months, hormonal treatment can be considered an effective and timely substitution for gonadotropin and testosterone insufficiency in cryptorchid infants. Therefore, we recommend this therapeutic procedure combined with surgery in the first year of life.

Age Factors↗
PubMed1996

ACTH and cortisol secretions in children with perinatal HIV-1 infection.

Serum cortisol and adrenocorticotropic hormone (ACTH) values and CD4 cell count were evaluated in 25 perinatally HIV-1-infected children. The children were divided into three groups: group 1 included eight asymptomatic or paucisymptomatic children, group 2 nine moderately symptomatic children, and group 3 eight children with severe clinical manifestations. Group 1 children were without antiretroviral therapy; the remaining children received zidovudine (AZT) treatment. Only one group 3 patient had primary adrenal insufficiency. No significant differences in cortisol and ACTH secretion were found either between all HIV-1-infected and 126 age- and sex-matched normal children or among the three groups of patients. Mean CD4 cell count of each group declined in parallel to disease progression. No correlations were found between cortisol or ACTH values and CD4 cell count. Adrenal failure may be a late complication of HIV-1 infection and should be searched for in severely ill patients. Our data argue against the hypothesis of a cortisol-induced shift from T-helper-1 (Th1) to Th2 cytokine production profile as the pathogenetic mechanism of progression to AIDS.

Adrenal Insufficiency↗
PubMed1995

Non-palpable testes. Orchiopexy in single stage.

From 1986 to 1990, 53 non-palpable testes were treated in the department of Pediatric Surgery and Endocrinology at the Regina Margherita Hospital, Turin, Italy. The reported patients were 45, 8 of them were bilateral with both testes non-palpable, 13 of the remaining patients were right cryptorchid and 24 were left. All patients received medical treatment, by LH-RH nasal spray and HCG, before surgery. None of the non-palpable testes descended by hormone therapy only, so that surgical exploration was always required. In the 53 reported cases, 10 gonads were not found, 13 were atrophic and 30 were abdominal. All abdominal gonads were positioned into the scrotum by orchiopexy in a single stage. Half of the patients underwent operation before the age of 2. Therefore, it is to be pointed out that the younger a patient the shorter his inguinal canal, this facilitates orchiopexy for high, undescended testes. In 10 patients a testicular biopsy was made during surgical procedure. Normal morphology and normal spermatogonia content were observed in the abdominal testes of the patients who had reached the age of 1 year. During the follow-up of the reported patients no upward displacement was observed. Eleven patients underwent postoperative testicular ultrasonography which showed that parenchymal structure of the operated testis was normal and the volume of the testis was slightly smaller than normal. Based on their experience, the authors suggest to correct cryptorchidism before the age of one year, surgical procedure follows immediately after ineffective hormone therapy.

Child, Preschool↗
PubMed1994

Growth impairment, IGF I hyposecretion and thyroid dysfunction in children with perinatal HIV-1 infection.

We evaluated the growth pattern, bone age, insulin-like growth factor I (IGF I) secretion and thyroid function in 24 perinatally infected children: 9 asymptomatic or paucisymptomatic (group 1) and 15 with a more advanced disease state and treated with zidovudine (group 2). Statural and ponderal growth were compared with those of 37 at-risk children who seroreverted. During the two-year follow-up, 22% of children in group 1 had impaired growth, 33% bone age delay, 45% reduced IGF I levels but none had thyroid dysfunction. In group 2, 53% had growth failure, 53% bone age delay, 86% reduced IGF I levels and 40% thyroid dysfunction. Among seroreverters, none showed growth impairment; statistically significant differences were found for height, weight and height velocity between perinatally infected children and seroreverters. Since auxological and hormonal evaluations run parallel to the clinical course of infection, these indices may be useful in monitoring disease progression.

Age Determination by Skeleton↗
PubMed1993

Combined therapy with LHRH and HCG in cryptorchid infants.

In 238 boys with cryptorchidism, between the ages of 4 and 48 months, luteinizing hormone releasing hormone (LHRH) was administered as nasal spray 1.2 mg/day for 4 weeks. The nonresponders received human chorionic gonadotropin (HCG) 500 I.U. i.m. three times a week for 3 weeks. With the combined treatment 37.8% of testes descended into the scrotum. Testicular descent occurred more often in patients whose testes were located in a lower position. Histological findings indicated a reduction in the number and maturation of germ cells. A clear improvement of germ cells trophism was observed in boys hormonally treated and operated on before the 12th month of life. Early administered combined treatment with LHRH and HCG can be considered as a substitution of the gonadotropins insufficiency manifested by most cryptorchid infants in the first months of life.

Administration, Intranasal↗
PubMed1992

Possible relationship between ulnar-mammary syndrome and split hand with aplasia of the ulna syndrome.

We describe a 3-generation family in which mother, maternal grandfather, and 2 (male and female) children have variably manifestations of the ulnar-mammary syndrome, including ulnar ray defects, obesity, hypogenitalism, delayed puberty, hypoplasia of nipples and apocrine glands, and a previously undescribed ectopia of upper canines. The index patient also had split-hand appearance on the right due to complete absence of the 4th ray. To our knowledge this is the first documented example of split hand in the ulnar-mammary syndrome. The hand anomaly raises the question of a possible causal relationship between ulnar-mammary syndrome and the split hand with aplasia of the ulna syndrome, as already hypothesized by Lenz [1980].

Abnormalities, Multiple↗
PubMed1992

New dysmorphic features in Rubinstein-Taybi syndrome.

We report a new case of Rubinstein-Taybi syndrome with a hypoplastic right kidney, persistent pulmonary hypertension, and mitral valve regurgitation. Other pertinent features included broad thumbs, broad big toes, syndactyly of the third and fourth fingers bilaterally, beaked nose, broad columella of the nose, patent ductus arteriosus, and motor and mental retardation. The testes were descended. The 3 month old patient had delayed motor and mental development corresponding to a 1 month old infant.

Humans↗
PubMed1991

Isolated adrenocorticotropic hormone deficiency associated with common variable immunodeficiency.

A 14-year-old girl has been suffering from an isolated adrenocorticotropin hormone (ACTH) deficiency with secondary glucocorticoid deficiency and common variable immunodeficiency since the age of 6.6 years. Human corticotropin releasing hormone administration did not increase ACTH and cortisol levels, strongly suggesting a pituitary deficiency. Despite the profound humoral defect, severe infections have never developed and the antibody response to herpes viruses was intact. We speculate that the association between two rare disorders, simultaneously diagnosed 2 months after measles, is not coincidental but caused by close interactions between neuro-endocrine and immune systems.

Adolescent↗
PubMed1990

Arginine potentiates the GHRH- but not the pyridostigmine-induced GH secretion in normal short children. Further evidence for a somatostatin suppressing effect of arginine.

To investigate the mechanism underlying the GH-releasing effect of arginine (ARG), we studied the interactions of ARG (0.5 g/kg infused i.v. over 30 min) with GHRH (1 microgram/kg i.v.) and with pyridostigmine (PD, 60 mg orally) on GH secretion in 15 children and adolescents with familial short stature (5.1-15.4 years). In a group of eight subjects ARG induced a GH increase not statistically different to that observed after GHRH (peak, mean +/- SEM: 38.0 +/- 10.4 vs 64.0 +/- 14.4 mU/l). The combined administration of ARG and GHRH led to GH levels (101 +/- 15.2 mU/l) higher than those observed after GHRH (P less than 0.025) or ARG alone (P less than 0.001) and overlapping with those recorded after combined PD and GHRH administration (111 +/- 22.4 mU/l). In the other seven subjects, ARG and PD administration induced a similar GH response either when administered alone (25.2 +/- 13.6 and 27.8 +/- 4.0 mU/l, respectively) or in combination (33.8 +/- 5.4 mU/l). In conclusion, our results show that in children ARG administration potentiates GHRH- but not PD-induced GH increase. These findings agree with the hypothesis that the GH-releasing effect of both ARG and PD is mediated via the same mechanism, namely, by suppression of endogeneous somatostatin release. Combined administration of either ARG or PD with GHRH has a similar striking GH-releasing effect which is clearly higher than that of GHRH alone.

Adolescent↗
PubMed1990

Heart-hand syndrome II. A report of Tabatznik syndrome with new findings.

The association of upper limb malformations and congenital cardiac anomalies was established as a definite clinical and genetic entity by Holt & Oram in 1960. Significant variability of malformations in both the upper limbs and the cardiovascular system has been well documented. In 1978, Temtamy & McKusick reported a family studied by Tabatznik, in which upper limb deformities, including type D brachydactyly, occurred in association with cardiac arrhythmias as a dominant, either autosomal or X-linked trait. They called this apparently new entity "Heart-Hand syndrome II" to distinguish it from the Holt-Oram syndrome. No other similar cases have subsequently been reported. We describe here the second family affected with the Tabatznik syndrome and add some new findings to the clinical spectrum of this condition.

Abnormalities, Multiple↗
PubMed1990

[Sex determination in ambiguous genitalia].

Choice of sex in children with ambiguous genitalia requires morphological evaluation of external and internal genitalia together with prevision of the kind of pubertal and psychosexual development. Female features in female pseudohermaphroditism, ambiguous in true hermaphroditism and mixed gonadal dysgenesis, male, ambiguous or female in male pseudohermaphroditism, are usually awaited. Increased risk of malignancy in poorly differentiated male gonads should be considered. In neonates diagnostic procedures should be urgently undertaken in order to choose correct sex as soon as possible. Parents must be convinced from the beginning in order to remove any possible doubt. There should be no change in sex, as a rule, after the second year of life, unless a strong psychosexuality arises in definite opposition to the sex so far assumed. In our experience, in 4 out of 23 cases with ambiguous genitalia, neonatal choice of female sex was refused by parents.

Disorders of Sex Development↗
PubMed1989

Endocrine involvement in mitochondrial encephalomyopathy with partial cytochrome c oxidase deficiency.

A 19-year-old man born with thyroprivic hypothyroidism, due to congenital development defect, manifested hypogonadism, stunted growth, chronic progressive external ophthalmoplegia (CPEO), diffuse muscle weakness and wasting, right bundle branch block, cerebral atrophy. Muscle biopsy showed mitochondrial abnormalities. Biochemical investigations on muscle disclosed partial (50%) cytochrome c oxidase deficiency, 58% decrease of cytochrome aa3 and 41% decrease of cytochrome b. Enzyme-linked immunosorbent assay showed decrease of the immunologically active enzyme protein.

Adult↗
PubMed1986

Teenage pregnancy in an urban hospital setting.

Recent research suggests that adverse consequences of teenage pregnancy are largely a function of social background factors and adequacy of prenatal care. This study examines the situation of young mothers with new babies in a low income, urban environment. The study explores the relationship between age and ethnicity and various life circumstance and life style differences which might effect long term developmental outcome. 475 Hispanic and black mothers were interviewed using a structured questionnaire. The majority are poorly educated, single parents. Educational attainment is higher for blacks than for Hispanics and for older mothers than for younger. Older mothers are more likely to be living with the father, to be married, and to have received adequate prenatal care. Hispanic parents are more likely than Blacks to be planning to live together. Hispanic mothers are more likely than blacks to be planning to be the primary caretaker for their babies. Adequacy of prenatal care is related to both prematurity and low birth weight. The implications of these findings are discussed in relation to pregnancy prevention and parenting education programs.

Adolescent↗