Mutation of the Thap4 gene causes dwarfism and testicular anomalies in rats and mice.

The petit (pet) locus is associated with dwarfism, testicular anomalies, severe thymic hypoplasia, and high postnatal lethality, which are inherited in autosomal recessive mode of inheritance in rats with a Wistar strain genetic background. Linkage analysis localized the pet locus between 98.7 Mb and 101.2 Mb on rat chromosome 9. Nucleotide sequence analysis identified 2 bp deletion in exon 2 of the Thap4 gene as the causative mutation for pet. This deletion causes a frameshift and premature termination codon, resulting in a truncated THAP4 protein lacking approximately two-thirds of the C-terminal side. Thap4 is expressed in various organs, including the testis and thymus in rats. To elucidate the biological function of THAP4 in other species, we generated Thap4 knockout mice lacking exon 2 of the Thap4 gene through genome editing. Thap4 knockout mice also exhibited dwarfism and small testis but did not show high postnatal lethality. Thymus weights of adult Thap4 knockout male mice were significantly higher compared to wild-type male mice. Although Thap4 knockout male mice were fertile, their testis contained seminiferous tubules with spermatogenesis and degenerative seminiferous tubules lacking germ cells. Additionally, we observed vacuoles in seminiferous tubules, and clusters of cells in the lumen in seminiferous tubules in Thap4 knockout male mice. These results demonstrate that spontaneous mutation of Thap4 gene in rats and knockout of Thap4 gene in mice both cause dwarfism and testicular anomalies. Thap4 gene in rats and mice is essential for normal testicular development, maintaining spermatogenesis throughout the entire region of seminiferous tubules.

Factors Influencing Quality of Life in Stroke Patients: Focus on Eating Habits.

BACKGROUND: Adherence to healthy lifestyle factors has been shown to improve outcomes after stroke. This study aimed to identify lifestyle factors about eating habits that may affect the quality of life (QOL) in elderly stroke patients. METHODS: Fifty elderly patients with a first-ever stroke were enrolled. QOL was assessed by the Stroke and Aphasia QOL Scale-39-J. Lifestyle factors about eating habits were collected using questionnaires (Questions 1-17) for the intake of salt, calcium, magnesium, potassium, taurine, fiber, and protein, and the frequency of breakfast. RESULTS: QOL of physical, communication, and psychosocial subdomains was better in the low (healthy) tertile of poststroke eating habits (Questions 1-17) compared with the high tertile of post-troke eating habits (Questions 1-17). This relationship appeared in eating habits except for salt intake but not in eating habits of salt intake and directly measured salt intake. Compared with prestroke eating habits score, poststroke eating habits score was decreased (improved) in 36 patients concerning eating habits of salt intake, but only in 12 patients concerning eating habits except for salt intake (P < .05 by chi-square test). Poststroke eating habits of calcium and magnesium were associated with better psychosocial QOL and better physical or energy QOL, respectively. CONCLUSIONS: Poststroke eating habits of calcium and magnesium were associated with QOL in elderly patients with a first-ever stroke. Since eating habits except for salt intake was poorly improved after stroke, intensive interventions regarding eating habits might be important.

Successful management of pregnancy and delivery in a woman with multiple coronary stenoses of unknown cause.

We describe the case of a 30-year-old primiparous woman who had multiple coronary stenoses of unknown cause, and discuss causes and risks in pregnancy in a patient with coronary stenoses and the management and outcome. At 13 years of age, the patient was diagnosed as having multiple coronary stenoses and percutaneous transluminal coronary angioplasty was performed. At the age of 30, coronary arteriography demonstrated multiple severe stenoses. Her previous physician had permitted her to become pregnant. At 32 weeks' gestation, due to uncontrollable uterine contractions, magnesium sulfate was administered. At 37 weeks' gestation, a cesarean section was performed because of breech presentation, and she delivered a healthy female infant. During cesarean section, oxytocin was given at a slower rate. There has been no recurrence of cardiac events during and after pregnancy. Multiple coronary stenoses during pregnancy need a multidisciplinary approach.

Postnatal development of hypoplastic thymus in semi-lethal dwarf pet/pet males.

The petit rat (pet/pet) is a new semi-lethal dwarf mutant with anomalies in the thymus and testes, defects inherited as a single autosomal recessive trait. At birth, these pet/pet rats show low birth weight and extremely small thymuses; at 140 days of age, their thymuses show abnormal involution. In the present study, we examined early postnatal development of hypoplastic pet/pet thymuses. In addition to being hypoplastic at birth, pet/pet thymus growth was almost completely impaired during the early postnatal period. As shown by cellular incorporation of BrdU, the mitotic activity was lower in pet/pet than in normal thymuses, and terminal deoxynucleotidyl transferase dUTP nick end labeling assays showed that apoptosis occurred more often in pet/pet than in normal thymus cells during the first few days after birth. These results indicate that postnatal development of the hypoplastic pet/pet thymus is defective due to the reduced proliferation and increased apoptosis of thymic cells.

The petit rat (pet/pet), a new semilethal mutant dwarf rat with thymic and testicular anomalies.

The petit rat (pet/pet) is a recently discovered semilethal mutant dwarf. The neonatal pet/pet rats had a low body weight and small thymus and testis. During the first 3 d after birth, 50% of the male and 80% of the female pet/pet pups were lost or found dead. Surviving pet/pet rats showed marked retardation of postnatal growth, and their body weights were 41% (female rats) and 32% (male rats) of those of normal rats at the adult stage. The pet/pet rats exhibited proportional dwarfism, and their longitudinal bones were shorter than those of controls without skeletal malformations. Most organs of male pet/pet rats, especially the thymus, testis, adipose tissue surrounding the kidney, and accessory sex organs, weighed markedly less at 140 d of age than did those of their normal counterparts. The thymus of pet/pet rats was small with abnormal thymic follicles. Testes from pet/pet rats exhibited 2 patterns of abnormal histology. Spermatogenesis was present in testes that were only slightly anomalous, but the seminiferous tubules were reduced in diameter. In severely affected testes, most of the seminiferous tubules showed degeneration, and interstitial tissue was increased. Plasma growth hormone concentrations did not differ between pet/pet and normal male rats. The dwarf phenotype of pet/pet rats was inherited as an autosomal recessive trait. These results indicate that the pet/pet rat has a semilethal growth-hormone-independent dwarf phenotype that is accompanied by thymic and testicular anomalies and low birth weight.

The influence of fluoride ingestion on urinary aluminum excretion in humans.

Fluoride (F) and aluminum (Al) are both ingested daily in water, foods, and pharmaceuticals. Owing to the strong chemical affinity between F and Al, these elements can interact in biological systems. The purpose of the present study was to investigate the influence of F ingestion on Al excretion in humans. Six healthy volunteers ingested 100 ml of distilled water at 6:00 a.m. on day 1 (control period) and the same volume of sodium fluoride solution containing 5 mg of F at 6:00 a.m. on day 2 (test period). A schedule for meals and for blood and urine collection was followed for the two successive days. The concentration of F was measured with an F-electrode, and Al was determined by ion-pair RP-HPLC with its complexation with 8-quinolinol. The mean concentration of serum F peaked within 30 minutes after ingestion of F and rapidly decreased thereafter, reaching baseline 24 hours later. In control period, there was no increase of Al concentration in serum in 24 hours. In test period, Al concentration in serum did not increase significantly compared with those in control serum. Although some variation was observed among subjects, cumulative amounts of F and Al excreted in urine during the test period were significantly higher than those during the control period. The results suggest that absorbed F enhanced urinary Al excretion and that the Al in urine may be, at least in part, derived from endogenous tissues.