Three siblings with Harlequin Ichthyosis in an Indian family.

The Harlequin fetus is a distinct genetic entity with a strikingly grotesque appearance. Three siblings (two males, one female) with Harlequin Ichthyosis, a rare form of congenital disorder, born to the same parents are presented. The genetic aspects are discussed and the relevant literature is reviewed.

Human chromosome Y and SRY.

The precise location of the SRY gene on the human Y chromosome has been revealed through studies of sex reversal cases involving deletion, cross-linking and mutations of the SRY gene. Its DNA sequence and mechanism of action are being understood. Similarity of SRY with Sry of mice and its interaction with other genes in male sex determination are discussed.

Incomplete gonadal dysgenesis.

A 21-year-old phenotypic male with ambiguous external genitalia and hypospadias was referred for cytogenetic studies. Exploratory laparotomy revealed presence of a small atropic uterus, unilateral gonadal dysgenesis with fallopian tubes on both sides and a cryptorchid testis on the left side. No gonad could be traced on the right side. Chromosomal analysis from peripheral whole blood culture revealed a 46,XY cell line. No mosaicism was detected. Endocrine studies showed elevated levels of serum FSH and LH with low borderline testosterone level and failure to respond to HCG stimulation. The presence of fallopian tube next to testis suggests absence of anti-Mullerian hormone secretion by Sertoli cells. The absence of Wolffian duct derivatives indicates insufficient secretion of testosterone by Leydig cells.

Serum lipoperoxide levels in surgical stress of abdominal hysterectomy.

In continuation of our studies on stress situations in female reproductive life span, serum lipid peroxide levels in terms of malondialdehyde (nmol/ml) have been determined in females [(n = 40) (aged between 35-40 years)] to undergo total abdominal hysterectomy (due to dysfunctional uterine bleeding). There occurred a statistically significant though within physiological limits, progressive rise in serum lipid peroxide levels right from preoperative stage 3.51, per operatively 3.56 to a maximum of 4.10 postoperative stage I with a tendency of fall at postoperative stage II 3.94 in comparison with self control on admission 2.97. It is suggestive of the balancing and protective role of scavenging enzyme system like superoxide dismutase also backed by improvement in health status of abdominal hysterectomy patients in terms of ambulation, free intake of food and behavioural positive attitude within 24 hours following operation presumably due to relief from stress of DUB. It is felt from the results of the present investigation that patients undergoing abdominal hysterectomy were free from free radical toxicity.

Polydactyly: a study of a five generation Indian family.

Preaxial polydactyly was observed in up to five generations of an Indian family living in a village in the Rajkot district (Gujarat). Among the 71 affected members, 45 were males and 26 were females. All these affected members showed preaxial polydactyly manifesting as a well formed, articulated extra digit of the hand or foot. Twenty other cases were also identified with polydactyly involving triphalangeal digits replacing the thumbs or duplication of the big toe(s). To the best of our knowledge, the present family is the largest in which several members have preaxial polydactyly of different types. No other abnormalities were apparent. The present study strongly suggests that preaxial polydactyly with a well formed extra digit, triphalangeal thumbs, and duplication of the big toe can be manifestations of the same autosomal dominant gene. It is likely that other factors are modifying the expression of this gene.

Translocation t(22;22)(p11.1;q11.1) and NOR studies in a female with a history of repeated fetal loss.

A 32-year-old phenotypic female with a history of nine consecutive abortions each in the first trimester was referred for cytogenetic studies. She was found to have 45,XX,t(22;22) (p11.1;q11.1) chromosomal pattern. The Ag-NOR banding technique showed that the NORs of both the acrocentrics involved in the translocation were deleted and the loss suffered from the elimination was compensated by the increased NOR activity as well as presence of dNOR on other acrocentric chromosomes.

Unilateral gonadal dysgenesis with both testis and fallopian tube on the same side in a 45,X/46,X inv (Y) mosaic male.

A 5-year-old male with ambiguous external genitalia, hypospadias and microphallus without an urethral orifice was referred for cytogenetic studies. Exploratory laparotomy revealed presence of an infantile uterus and unilateral gonadal dysgenesis with both testes and fallopian tube on the right side. The metaphase cells from peripheral blood culture showed both 45,X/46,X inverted Y (p11.2q11.23) cell-lines (98:2). The inverted Y was found to be of paternal origin. Maternal chromosomal pattern was normal 46,XX. The presence of a fallopian tube next to testis suggest absence of secretion of anti-Mullerian hormone by Sertoli cells. The absence of Wolffian duct derivatives suggest insufficient secretion of testosterone by Leydig cells.

Serum lipoperoxides in induced and spontaneous abortions.

Abortion, primarily as a measure of population control, certainly continues to be an emotional, frustrating and stressful event. In continuation of our work on stressful situations in the female life span and biochemical parameters, serum lipid peroxide levels in terms of malondialdehyde (nmol/ml) have been determined in females undergoing abortion [suction curettage (n = 30), Emcredil-induced abortion (n = 30) and spontaneous abortion (n = 40)] and were compared with appropriate gestational controls. Irrespective of the type of abortion, the serum lipid peroxide levels before abortion [mean malondialdehyde concentrations (nmol/ml): suction curettage 2.67, Emcredil-induced abortion 3.22, and spontaneous abortion 3.49] were found to be significantly elevated in comparison with those after abortion (suction curettage 1.91, Emcredil 1.97 and spontaneous abortion 1.95), indicating a maximum at peak time of stress and a minimum at the end of stress. The levels of serum lipid peroxide encountered before abortion were found to be significantly elevated in case of Emcredil-induced abortion and spontaneous abortion when compared with controls (second trimester mean levels 1.82 and first trimester 2.4) whereas the levels before suction curettage were found to be nonsignificant in comparison with controls, indicating a lesser degree of stress. It is felt that monitoring of serum lipid peroxide levels in serum and tissues (placenta), backed by scavenging enzyme superoxide dismutase, can be more helpful for corroborating safety and the risk of free radical toxicity in pregnancy and abortion.

PIP: Abortion, primarily as a measure of population control, continues to be an emotional, frustrating, and stressful event. As an extension of the work the authors have done on stressful situations in the lifespan of the female and its biochemical parameters, serum lipid peroxide levels in terms of malondialdehyde (nmol/mI) have been determined in women undergoing abortion (n=30 for suction curettage), Emcredil-induced abortion (n-30), and spontaneous abortion (n-40) and were compared with appropriate gestational controls. Regardless of the type of abortion, the serum lipid peroxide levels before abortion (mean malondialdehyde concentrations [nmol/ml]: suction curettage 2.67, Emcredil-induced abortion 3.22, and spontaneous abortion 3.49) were significantly elevated in comparison with those after abortion (suction curettage 1.91, Emcredil 1.97, and spontaneous abortion 1.95), indicating a maximum at peak time of stress and a minimum at the end of stress. Levels of serum lipid peroxide encountered prior to abortion were significantly elevated in cases of Emcredil-induced abortion and spontaneous abortion when compared with controls (2nd trimester mean levels 1.82 and 1st trimester 2.4), whereas the levels prior to suction curettage were nonsignificant in comparison with controls. This indicates a lesser degree of stress. It was decided that monitoring of serum lipid peroxide levels in serum and tissues (placenta), backed up by scavenging enzyme superoxide dismutase, can be more helpful in corroborating safety and the risk of free radical toxicity in pregnancy and abortion.

Analysis of the functional and nuclear integrity of human spermatozoa.

The analysis of semen quality and sperm function has added a new dimension to the evaluation of male infertility. In the present investigation, some recent techniques were used to assess the nuclear, membrane, and acrosomal integrity of spermatozoa from semen of 15 subfertile males with low sperm count and motility. In the infertile semen, the live-to-dead ratio and percentage of spermatozoa showing swelling in hypoosmotic solution was lower than normal but correlated positively with the motility of spermatozoa (r = .85). Staining the spermatozoa with silver nitrate, using a modified technique developed in our laboratory, revealed a higher percentage of morphologically abnormal spermatozoa, in particular, with loss of acrosomal integrity in the subfertile males. Moreover, the percentage of green-fluorescing "fertile" spermatozoa, with intact double-stranded DNA (acridine orange fluorescence), was lower than normal, which correlated with the reduction in sperm nuclear DNA content. A low correlation was obtained between motility and the percentage abnormal spermatozoa (r = .44) and motility and percent green sperm (r = -.28), suggesting that both tests evaluate sperm functional properties independent of motility. The new parameters, assessed with recent techniques, indicate poor sperm fertilizability, which may therefore contribute to the low fertility of the cases studied.

A triple-X female with long arm deletion of one of the X-chromosomes associated with primary amenorrhoea: 47,XX, +del(X) (q27.3).

A 25-year-old phenotypic female with primary amenorrhoea was referred for chromosomal analysis. Earlier she had undergone hormonal therapy but showed no response. The secondary sex characters were of female type, with poor breast development. Laparoscopic findings revealed the presence of a very small uterus; the right ovary was found to be undeveloped and the left was absent. Cytogenetic study revealed a case of triple-X with deletion of the terminal region of the long arm of one of the X chromosomes [Xq27.3]. Among the 100 buccal mucosa cells analysed, 30 cells showed double Barr bodies. Hormonal studies using RIA technique revealed normal levels of prolactin (9.1 ng/ml), a high level of FSH and LH (135 and 61 mIU/ml) and low levels of estradiol and progesterone (12 pg/ml and 0.20 ng/ml respectively). To our knowledge, this may be the first report of a triple X with deletion of the X chromosome associated with primary amenorrhoea.

Serum immunoglobulin status of psychiatric in-patients.

In view of the fact that substantial evidence today links psyche, brain, stress and immune system, the serum immunoglobulin (viz. IgG, IgA, IgM) levels in 40 patients with psychiatric disorders (viz. Schizophrenia, Affective disorder and generalized Anxiety disorders) have been investigated. With the exception of IgA, all psychiatric patients had significantly elevated IgG, IgM levels (p less than 0.001) when compared with healthy controls. Surprisingly these immunoglobulin levels irrespective of prevalent psychiatric disorder were almost similar to those of the hospitalized surgical patients pre-operatively (preferable controls), suggestive of no direct linear causal relationship between the psychiatric disorder and serum immunoglobulin levels. Factors affecting immunoglobulins have been discussed. Considering a probable viral association in Schizophrenia it is felt that simultaneous monitoring of viruses (affecting the nervous system) in the form of antigen/antibodies may be more informative.

Cytogenetic studies in a population suspected to have chromosomal abnormalities.

The present study describes the cytogenetic findings in cases suspected with chromosomal abnormalities, in cases of mental retardation, multiple congenital malformations, clinical features of Down's syndrome, Klinefelter's syndrome, Turner's syndrome, ambiguous sex, sterility, amenorrhea and history of repeated spontaneous abortions in couples. Cytogenetic studies were done in 144 of the total 205 cases. In all, 57 (39.58%) were shown to have chromosomal abnormality and of these, 34 cases (25.7%) were Down's syndrome. Sex chromosome abnormality was found in 19 cases (13.2%). The results confirm the significant contribution of chromosomal abnormalities in the genesis of mental retardation, and abnormal sexual development.

Serum lipoperoxide levels in pregnancy induced hypertension.

With present day awareness of role and toxicity of lipid peroxides, serum levels of lipoperoxides have been investigated in forty pregnancy induced hypertension (PIH) subjects, before and after antihypertensive drug therapy, using full term normotensive patients as control. PIH subjects demonstrated highly significant elevated serum levels of lipoperoxides (mean 3.60 nmol/ml) in comparison (mean 2.15 nmol/ml) with full term normotensive subjects. At post-partum PIH subjects following antihypertensive drug therapy and becoming normotensive showed highly significant fall in serum lipoperoxide (mean level 2.27 nmol/ml). Full term normotensive subjects at post-partum also demonstrated the same pattern. However, observed levels of serum lipoperoxide in PIH subjects at post-partum even after becoming normotensive following treatment were found to be significantly elevated when compared with those of full term normotensives at post-partum (mean level 1.94 nmol/ml). It is felt that monitoring of serum lipoperoxide level can serve as one of the useful parameters in PIH subjects.

Chonemorphine, stigmasterol, and ecdysterone: steroids isolated through bioassay-directed plant screening programs.

In a bioassay-directed screening programme of plants for the identification of active constituents the following steroids were isolated. Chonemorphine was identified as the antiamoebic and antitrichomonad principle of Chonemorpha fragrans. Stigmasterol from Coleus forskohlii and ecdysterone from Diploclisia glaucescens were inactive constituents isolated during the process of purifying the active principles of the plants. D. glaucescens roots are a high-yielding source (0.5% of the dry root weight) of ecdysterone.

Inherited pericentric inversion of Y-chromosome with trisomy 21. A case report.

A 13-year-old boy with clinical features of Down syndrome was investigated. His karyotype was 47,X,inv(Y),+21. The proband's father and two elder brothers were also found to have the inv(Y). A spontaneous chromatid break was observed in the long arm of the X chromosome[? fra (X)] in 2% of the cells. The mother had two spontaneous abortions. This is the first case of trisomy-21 with inv(Y) in our population. This finding might be fortuitous. The frequency of inv(Y) in Down syndrome is not known.

Genotoxic effects of MeCCNU on human peripheral blood lymphocytes.

MeCCNU (semustine, 1-(2-chloroethyl)-3-(4-methylcyclohexyl)-1-nitrosourea, NSC 95441) is successfully used in the treatment of various human malignancies. The drug was tested for its in vitro genotoxic effects on human peripheral blood lymphocytes. Several drug concentrations were studied considering mean plasma level achieved in patients after the receipt of MeCCNU therapy. Induction of chromosome aberrations and sister chromatid exchange frequency had shown dose-effect relationship. Reduced mitotic activity and prolonged average generation time was observed in MeCCNU treated cultures. The results suggest that 'therapeutic' MeCCNU concentrations have genotoxic effects on human peripheral blood lymphocytes.

Effects of CCNU therapy on human chromosomes.

Peripheral blood lymphocytes of 9 patients under CCNU therapy were examined for frequency of sister-chromatid exchanges (SCEs) and chromosomal aberrations (CAs). 7 out of 9 patients were treated with only CCNU, whereas the remaining 2 were treated with other chemotherapeutic agents in combination with CCNU. Compared to normal individuals, a significantly increased frequency of SCE was observed in the patients before starting anticancer therapy (P less than 0.001). Increased incidences of structural changes in chromosomes were observed in cells from all the treated patients. The most frequent aberrations were of chromatid type. After administration of a single dose of CCNU, an increase in SCE frequencies was observed which remained elevated even after 6 weeks. It was concluded that increases in SCEs and CAs in lymphocytes were caused by CCNU treatment. Further studies are needed to elucidate whether any CAs observed in the present study could participate in the induction of second neoplasm.