Elevated Serum Growth Hormone Accelerates Gastric Tumorigenesis in F344 Rats after Treatment with N-Methyl-N-nitrosourea in Their Drinking Water

We examined the effects of growth hormone on tumorigenesis in F344 rats treated with N -methyl- N -nitrosourea (MNU). Four-week-old male F344 rats were exposed to 100 ppm MNU in their drinking water for 15 weeks. Thereafter Group II animals received 100 μCi/100 g body weight of ¹³¹I (radiothyroidectomy, Tx) injected i.p. and Group III rats were implanted with pituitary tumors (MtT) secreting growth hormone while Group I received no further treatment after MNU. Non-carcinogen control animals received MtT, Tx or no treatment. Animals were killed at 39 weeks after starting MNU administration. Gastric tumors were present in 13 of 31 (43%), 15 of 32 (47%) and 17 of 32 (53%) rats in Groups I to III, respectively. All tumors were of well-differentiated type. Spinal cord tumors appeared in 15 of 31 (47%) in Group I, 10 of 32 (32%) in Group II and 10 of 32 (32%) in Group III, most being malignant schwannomas. Thymic lymphornas also appeared in 10 of 31 (32%), 5 of 32 (16%) and 6 of 32 (19%) animals in Groups I to III, respectively. There were no significant differences among the groups. However, tumors in Group III developed significantly earlier than in Groups I or II. This was mainly due to gastric tumors, and cumulative incidence curves for spinal cord tumors or thymic lymphomas were similar in all groups. The results indicate that gastric tumors induced by MNU in F344 male rats are influenced by elevated levels of growth hormone.     

An Outbreak of Echovirus 11 Meningitis in a Newborn Nursery

In the summer of 1981 an outbreak of echovirus 11 meningitis in a newborn nursery occurred in a general hospital near Tokyo. Ten newborn infants developed febrile illness in a period of 20 days. Nine babies out of ten were diagnosed as aseptic meningitis according to the CSF findings. Virus isolation was successful in 50% (3/6 cases) in the CSF, 80% (4/5 cases) in the stool and 20% (1/5 cases) in the throat swab. Echovirus 11 was proven to be the responsible agent. Clinical manifestations of aseptic meningitis were mild and nonspecific, except in one premature baby which had apnea and exanthema. Mean febrile period was 4.1 days. Pleocytosis of the CSF, dominant in polymorphonuclear cells, was observed in 6/9 cases. EEG about one month after onset revealed abnormal or borderline findings in 6/9 cases. In a community outbreak of echovirus. infection, newborn babies in nurseries are threatened with both horizontol and vertical transmission of virus.     

Analysis of Thyrotropin-Thyroxine Secretory Dynamics in Infantile Hyperthyrotropinemia: An Aid for Early Differential Diagnosis

For the purpose of differentiating neonatal hyperthyrotropinemia, the interrelation between serum thyrotropin (TSH) and thyroxine (T4) was examined in 10 infants with primary hypothyroidism during 12 months of T4 replacement therapy. A significant inverse correlation was obtained between elevated TSH (Y) (above 12 μU/ml) and T4 (X) levels; Y = 324 - 22 X (r = -0.801, p < 0.001). One patient had an abnormally high threshold of TSH-inhibition by T4. Based on this regression line, a scattergram of TSH-T4 correlation and changes in the time course was analyzed in 13 infants with neonatal hyperthyrotropinemia, including eight with transient hyperthyrotropinemia (t-TSH), three with compensated hypothyroidism (c-Hypo) and two with transient hypothyroidism (t-Hypo). All plots from t-TSH were distributed under the regression line and shifted downward with concomitant rise in T4 and free T4 levels. In contrast, plots from c-Hypo and t-Hypo showed a vertical upward shift above the line during 3–4 months of observation without treatment. These results indicate that (1) using the TSH-T4 regression line, differentiation of c-Hypo from t-TSH is possible by 3 months of age, (2) the cause of t-TSH is not an elevated threshold for TSH release, but rather the maturational delay in responsiveness of the thyroid to TSH, and (3) suppression of TSH alone should not be used as the index of adequate T4 dose in infantile hypothyroidism, because of the existence of patients with a high threshold of TSH-inhibition by T4.     

Influence of Paternal 252Cf Neutron Exposure on Abnormal Sperm, Embryonal Lethality, and Liver Tumorigenesis in the F1 Offspring of Mice

Experiments were conducted to determine whether neutron-induced genetic damage in parental germline cells can lead to the development of cancer in the offspring. Seven-week-old C3H male mice were irradiated with ²⁵²Cf neutrons at a dose of 0, 50, 100, or 200 cGy. Two weeks or 3 months after irradiation, the male mice were mated with virgin 9-week-old C57BL females. Two weeks after irradiation, the irradiated male mice showed an increased incidence of sperm abnormalities, which led to embryo lethalities in a dose-dependent manner when they were mated with unirradiated female mice. Furthermore, liver tumors in male offspring of male mice in the 50 cGy group were significantly increased in 19 of 44 (43.2%) animals, in clear contrast to the unirradiated group (1 of 31; 3.2%) ( P < 0.01). In the 100 cGy group, 6 of 39 (15%) mice had lesions. At 3 months after irradiation abnormal sperm and embryonal lethality were not significantly increased. The incidences of liver tumors in male offspring from the 50 cGy, 100 cGy and 200 cGy groups were 6 of 20 (30%), 5 of 22 (23%) and 1 of 19 (5%), respectively, which are not significantly increased compared with the control. It is concluded that increased hepatic tumor risk in the F₁ generation may be caused by genetic transmission of hepatoma-associated trait(s) induced by ²⁵²Cf neutron irradiation.     

Effects of prolactin on gametes and zygotes during in vitro fertilization in mice

Hyperprolactinemia is one of the major causative factors of infertility. However, the effect of prolactin on gametes during in vitro fertilization has not been elucidated. In the present study, the effects of mouse prolactin on the motility of spermatozoa, in vitro fertilization, and in vitro development of the zygote were investigated in mice using media containing three different concentrations (10, 50, and 100 ng/ml) of mouse prolactin. The development of unfertilized and fertilized oocytes (zygotes) was not affected in vitro by prolactin regardless of the amount of prolactin added to culture media. However, the fertilizing capacity of the spermatozoa was suppressed when they were preincubated for 90 min in culture media containing prolactin at concentrations of 50 and 100 ng/ml. The motility of spermatozoa was not affected by prolactin regardless of the concentration of prolactin used for preincubation. The present study indicates that prolactin may have some effects on the capacitation process of spermatozoa in vitro. This result should be taken into consideration in in vitro fertilization and embryo transfer procedures in humans.     

Effects of growth hormone on testicular dysfunction induced by cyclophosphamide (CP) in GH-deficient rats

Growth hormone (GH) is known to accelerate spermatogenesis and maintain gonadal function. In this study, we evaluated the effect of GH on recovery from testicular damage induced by cyclophosphamide (CP). Eleven- to fourteen-week-old GH-deficient Lewis rats (dw/dw) were divided into 4 groups (n = 10 each), with one group serving as controls. In the CP group, CP was intravenously administered in daily doses of 50 mg/kg for 2 days, followed by daily doses of 10 mg/kg for the next 3 days. In the GH group, rat GH was subcutaneously administered at a daily dose of 0.3 mg/kg until the rats were sacrificed. In the CP/GH group, GH and CP administration were started simultaneously. In the CP/preGH group, GH administration was started 14 days before CP administration. Five rats from each group were sacrificed at days 14 and 28 after administration of CP. Spermatogenesis was then evaluated morphometrically by counting numbers of cells at several stages of the spermatogenic cycle. On day 14, there were no significant differences in the numbers of the spermatocytes between CP and CP/GH group. On day 28, the numbers of spermatocytes and motility of spermatozoa in CP/GH group were greater than those of CP group were. In the CP/preGH group, these effects of GH administration were not observed. These results suggested that administration of GH improved testicular function damaged by CP under GH-deficient condition, when GH and CP administration are started simultaneously.     

Complete penetration of the optic chiasm by an unruptured aneurysm of the ophthalmic segment: case report

BACKGROUND: It is well known that aneurysms of the ophthalmic segment sometimes elevate the optic nerve or chiasm, and in case of large or giant aneurysms, the optic apparatus can be dramatically thinned. Nonetheless, they rarely penetrate the optic pathway completely. To our knowledge, no previous reports have dealt with the complete penetration of the optic chiasm by unruptured aneurysms of the ophthalmic segment. CASE DESCRIPTION: A 70-year-old woman presented with visual dysfunction in her left eye that she had experienced for several months. Her left visual acuity had rapidly deteriorated to the level of finger counting and visual field testing demonstrated nasal hemianopsia in the left eye and upper temporal quadrant hemianopsia in the right eye. Left internal carotid angiograms and three-dimensional digital subtraction angiograms showed an aneurysm of the ophthalmic segment projecting superomedially. Intraoperative findings revealed complete penetration of the optic chiasm by the fundus of the aneurysm. The optic pathway adjacent to the dome had become remarkably thin and dark yellow. After clipping was completed, the fundus of the aneurysm was punctured to decompress the optic chiasm. Postoperatively, patient's visual acuity in the left eye gradually recovered, but the visual field deficit persisted after the operation. CONCLUSION: This rare case demonstrates the potentially aggressive behavior of unruptured aneurysms of the ophthalmic segment. Patients with unruptured aneurysms of the ophthalmic segment who present with visual symptoms should be treated with surgical clipping to decompress the optic pathway as soon as possible.     

Improvement of muscle healing through enhancement of muscle regeneration and prevention of fibrosis

Skeletal muscle is able to repair itself through regeneration. However, an injured muscle often does not fully recover its strength because complete muscle regeneration is hindered by the development of fibrosis. Biological approaches to improve muscle healing by enhancing muscle regeneration and reducing the formation of fibrosis are being investigated. Previously, we have determined that insulin-like growth factor-1 (IGF-1) can improve muscle regeneration in injured muscle. We also have investigated the use of an antifibrotic agent, decorin, to reduce muscle fibrosis following injury. The aim of this study was to combine these two therapeutic methods in an attempt to develop a new biological approach to promote efficient healing and recovery of strength after muscle injuries. Our findings indicate that further improvement in the healing of muscle lacerations is attained histologically by the combined administration of IGF-1 to enhance muscle regeneration and decorin to reduce the formation of fibrosis. This improvement was not associated with improved responses to physiological testing, at least at the time-points tested in this study.     

Steroid effects on vestibular compensation in human

Vestibular neuritis (VN) rapidly damages unilateral vestibular periphery, inducing severe balance disorders. In most cases, such vestibular imbalance is gradually restored to within the normal level after clinical therapies. This successive clinical recovery occurs due to regeneration of vestibular periphery and/or accomplishment of central vestibular compensation. We experienced 36 patients with VN treated at our hospital, including cases in our previous preliminary report. To elucidate effects of steroid therapy both on the recovery of peripheral function and on the adaptation of central vestibular compensation, we examined caloric test and several questionnaires with two randomly divided groups, 18 steroid-treated and 18 nonsteroid-treated patients, over two years after the onset. These examinations revealed that steroid-treated patients had a tendency of better canal improvements (13/18, 72%) than nonsteroid-treated ones (10/18, 55.6%). However, there was no significant difference between these two groups. In cases with persistent canal paresis, steroid-treated patients (n = 5) reduced handicaps in their everyday life due to the dizziness induced by head and/or body movements and the disturbance of their mood, more effectively than those with nonsteroid therapy (n = 8). These findings suggest that steroid therapy with VN could be effective on not only vestibular periphery but central vestibular system, to restore the balance.