Mapping the locus of the H-Y gene on the human Y chromosome.

The H-Y locus is on the short arm of the human Y chromosome in most individuals but on the long arm in at least one of 17 individuals with structural abnormalities of the Y.

Effect of vincristine on sister chromatid exchanges of normal human lymphocytes.

In vitro analysis of the mitosis from 3-day lymphocyte cultures from two normal males and two normal females treated with bromodeoxyuridine and stained with acridine orange after addition of vincristine during different times demonstrated that vincristine inhibits the progression of the second division. When the second division progressed, the number of sister chromatid exchanges was significantly decreased. Vincristine could act by inhibiting the copying of DNA. A dosage effect is demonstrated when vincristine is added to the cultures during the first 24 hr.

Atlantoaxial malformation in a 46,XY, 17q+ child.

A child with 46,XY, 17q+ chromosome aberration and unusual skeletal abnormalities had the presenting symptom of respiratory arrest after a fall and minor head trauma. He exhibited proportionate short stature, peculiar facies with antimongoloid slant, simian creases, postaxial hexadactyly, metatarsus adductus deformity, and anomalous penoscrotal configuration. Delayed speech and mild mental retardation were also present. Atlantoaxial dislocation secondary to odontoid process hypoplasia was demonstrated. Additional skeletal abnormalities included dysplastic changes in the first and fourth metacarpals, the middle phalanx of the second finger, and hypoplasia of the first metatarsal, with medial insertion of the great toe. Treatment consisted of halo jacket cast and fusion of the occiput to C1, C2, and C3. Early detection and preventive surgery for atlantoaxial dislocation is necessary to prevent neurological deficit and possibly death by respiratory failure.

Segregation analysis in reciprocal translocation carriers.

Segregation analysis of the offspring of balanced translocation carriers was performed on 327 pedigrees collated from published sources and personal communications. Correction was made for bias of ascertainment. Translocations studied involved chromosome arms 1p, 4q, 6p, 6q, 7p, 8p, 10p, 10q, 11q, 14q, 16q, and 17p. Findings included similar rates of occurrence of abnormal liveborn offspring in male and female carriers except for a reduction of risk in male carriers of translocations segregating by 3:1 mode; an elevated risk of fetal loss (spontaneous abortions and stillbirths) in female carriers of 6q, 11q, and 16q translocations compared to male carriers of these translocations; a fetal loss rate exceeding general population estimates in female carriers of 6q and 10q translocations and in male carriers of 6p, 8p, 10q, and 14q translocations including a rate of nearly 50% among female 6q translocation carriers; a higher than expected number of balanced carriers among liveborn offspring; and a low risk of abnormal liveborn children among carriers ascertained by means other than through unbalanced probands. We propose that some translocation carriers may be helped by consideration of more specific empiric risk figures than have traditionally been used.

Complex chromosome 4, 9, and 22 rearrangement in a patient presenting with AML-FAB M2.

Fluorescence in situ hybridization (FISH) and the reverse transcription-polymerase chain reaction (RT-PCR) were used to examine a patient presenting with acute myelogenous leukemia (AML) FAB M2, and a complex t(4;9;22)(p14;q34;q11.2). The patient's clinical course was characterized by an aggressive leukemia, resistant to intensive therapy including allogeneic bone marrow transplantation. FISH analysis, using two chromosome painting probes and a BCR/ABL specific probe, confirmed the cytogenetic observation of a 22q11.2-->4p14 and a 4p14-->9q34 exchange, and revealed the presence of a 9q34-->22q11.2, respectively. In addition, RT-PCR demonstrated the presence of a BCR/ABL transcript derived from the major breakpoint cluster region (M-bcr) of the BCR gene. This transcript has been shown to generate an active 210 kDa tyrosine kinase protein more commonly observed in chronic myelogenous leukemia. Because the presentation of AML with this ABL-->BCR fusion product is a rare event, it would seem likely that the additional complex chromosomal rearrangement involving chromosomes 4, 9, and 22 played a role in the aggressive presentation and clinical behavior of this patient's leukemia.

Treatment of cryptorchidism. Long-term prospective study.

We have presented preliminary findings on a long-term prospective study designed to (1) assess timing of orchiopexy, (2) eliminate unnecessary abdominal exploratory surgery, and (3) determine efficacy of orchiopexy on subsequent fertility and on malignant degeneration. Some suggestions for the management of this common congenital defect can be provided, but long-term results are lacking. A significant drop-out rate from this prospective study is expected with time; therefore, large patient numbers are needed to draw any valid conclusions at the time of postpubertal reassessment.

Pituitary function in adult males receiving medroxyprogesterone acetate.

The pituitary, adrenal, and gonadal functions of nine males (six XY, two XYY, and one XY/XYY) were studied after at least 6 months of medroxyprogesterone acetate (MPA) therapy for antisocial or sex-offending behavior. Five were studied both before and during therapy, four only during therapy. MPA was effective in decreasing serum gonadotropin and plasma testosterone concentrations. MPA caused no change in the 24-hour rhythm or total integrated concentration of growth hormone. The plasma cortisol circadian rhythm was suppressed but not obliterated by MPA therapy. Although a significant decrease (P less than 0.001) in 24-hour integrated concentrations of plasma cortisol was also found, the rise in the plasma cortisol level after insulin-induced hypoglycemia was unchanged.