Intrinsic and extrinsic regulation of the proliferation and differentiation of cells in the rodent rostral migratory stream

An overriding principle of development is that neurons become permanently postmitotic once they initiate differentiation. Work in our laboratory, however, has provided evidence for a population of progenitor cells in mammalian forebrain that express properties of differentiated neurons, even though they continue to divide. These neuronal progenitor cells are situated in the rostral migratory stream (RMS), which extends from a specialized portion of the subventricular zone surrounding the anterior tip of the lateral ventricle, referred to as the SVZa, to the middle of the olfactory bulb. As SVZa-derived cells migrate to the olfactory bulb, they undergo cell division, and they never deviate from the RMS. Once they reach their final destinations, they become terminally postmitotic interneurons. This Mini-Review concerns findings from our recent experiments designed to reveal the intrinsic and extrinsic mechanisms governing the proliferation and differentiation of the unique SVZa neuronal progenitor cells. We have investigated the role(s) of cell cycle regulatory proteins, in particular, the cell cycle inhibitor p19(INK4d), in the control of SVZa cell proliferation. Several studies have indicated that cells withdraw from the cell cycle once they express p19(INK4d). To begin to investigate whether p19(INK4d)(+) SVZa-derived cells are postmitotic, we analyzed the pattern of p19(INK4d) expression by the cells of the RMS. A pronounced gradient of p19(INK4d) expression was demonstrated; progressively more cells are p19(INK4d) immunoreactive as the olfactory bulb is approached. In addition, the capacity of p19(INK4d)(+) cells to incorporate bromodeoxyuridine was investigated. From the results of these studies, we conclude that SVZa cells in the RMS can successively down-regulate their expression of p19(INK4d) as they migrate and that they repeatedly exit and reenter the cell cycle while en route to the olfactory bulb. These studies led us to investigate whether bone morphogenetic proteins (BMPs) are involved in the regulation of SVZa cell proliferation and p19(INK4d) expression, because, elsewhere in the CNS, BMPs modulate cell proliferation and influence cell fate decisions. To determine the effects of BMP signaling on SVZa cell proliferation and differentiation, we altered the expression of the BMP receptor Ia (BMPR-Ia) using retrovirally mediated gene transfer. The cells in the SVZa encoding the wild-type BMPR-Ia exit the cell cycle and do not appear to migrate through the RMS. Conversely, both within the SVZa and along the RMS, the majority of SVZa-derived cells encoding a dominant-negative BMPR-Ia gene do not express p19(INK4d). These findings indicate that p19(INK4d) expression is suppressed when BMP signaling is inhibited. Furthermore, SVZa-derived cells with both augmented and inhibited BMP signaling retain their neuronal commitment. Collectively, these studies have revealed that SVZa cell proliferation and differentiation is under the control of several interacting intrinsic and extrinsic factors.     

Tamoxifen therapy and hepatic steatosis

Tamoxifen has been used for a long time as a hormonal treatment in breast cancer. Recent studies in pre and postmenopausal women have shown that tamoxifen exhibits favorable effects on the lipid profile. In this study we investigated the effects of tamoxifen on lipid profile and hepatic steatosis. Fifty two (31 postmenopausal and 21 premenopausal) women with breast cancer treated with tamoxifen at a dose of 20 mg daily were included in the study. Serum lipid parameters (total cholesterol, high and low density lipoprotein cholesterol and triglyceride) were measured baseline and at the 6th month of tamoxifen treatment. Upper abdominal ultrasonography was performed before and at the 6th month of therapy for assessment of liver steatosis. We obtained decreased levels of serum total cholesterol after 6 months of tamoxifen treatment (p < 0.05). However, we did not detect any changes in triglyceride and high-density lipoprotein cholesterol levels (p > 0.05). Increased liver steatosis was observed in 22 patients (42.3%) after tamoxifen treatment. We could not detect increase in lipid levels in these patients. There was no significant difference between the lipid levels in the patients with increased liver steatosis and stable or no liver steatosis. Whether hepatic steatosis is dependent on lipid changes in tamoxifen use should be further investigated.     

Rotational vertebro-basilar insufficiency secondary to a fibrous band of the longus colli muscle: value of CT spiral angiography diagnosis

A CASE REPORT: The authors report a case of rotational vertebro-basilar insufficiency causing "drop-attacks". To our knowledge, it is the first case of extraluminal vertebral artery compression caused by a fibrous band of the longus colli muscle, demonstrated by spiral computed tomographic angiography with volume rendering reformation.     

Balloon-assisted ultrasound-guided direct percutaneous embolization of a peripheral pseudoaneurysm with n-butyl cyanoacrylate

We report the ultrasound-guided direct percutaneous injection of n-butyl cyanoacrylate to embolize an iatrogenic peripheral pseudoaneurysm secondary in a 33-year-old patient undergoing hemodialysis. We protected the parent artery with inflation of an angioplasty balloon across the neck during the cyanoacrylate injection. Complete occlusion of the pseudoaneurysm was achieved without ischemic complication.     

The effects of one- and two-stage orchiopexy on postoperative serum testosterone levels and testicular volume in adult patients with bilateral nonpalpable testes

In this study, we investigated the effects of one- and two-staged orchiopexy on testicular volume and serum testosterone levels in cases with high, abdominally localized, bilateral nonpalpable testes. Between March 1996 and April 2001, orchiopexy was performed on 46 testes in 23 patients with bilateral nonpalpable testes. In 15 of the 23 patients, a two-stage Fowler-Stephens orchiopexy was performed, and in 8 of the 23 patients, a one-stage laparoscopic orchiopexy was performed. For one patient who lacked both testes, bilateral prosthetic testes were inserted. The patients' ages were between 20 and 23 years (average, 21 years). In the first stage of the two-stage orchiopexy, the spermatic artery was ligated laparoscopically. Six months later, open surgery orchiopexy was performed. Patients were followed for 2 to 16 months (average, 10 months) and were evaluated for testicular atrophy, serum testosterone levels, and complications. In all the patients, the preoperative secondary sexual characteristics and serum testosterone levels were normal. Among the postoperative controls, evaluated at months 3 and 6, one patient's testes were found at the pubic area. Testicular atrophy was not observed in any of the patients, and the serum testosterone levels were in the normal range. In the two-stage orchiopexy group, 5 (33%) of the 15 patients had an average 30% volume decrease, and in the one-stage group, 2 (25%) of the 8 patients had an average 40% volume decrease. In this study, it was shown that either two-stage Fowler-Stephens orchiopexy or laparoscopic orchiopexy can be successfully performed in patients with bilateral abdominal testes, and that the testes can be fixed to their palpable original positions without interfering with the secretion of testosterone. Although the results are similar, our experience suggests that single-stage laparoscopic orchiopexy is the preferable method.     

Dizygotic twins with schizencephaly and focal cortical dysplasia

The case reports of 17-year-old female dizygotic twins are presented. One of the twins had bilateral closed-lip schizencephaly, and the other had focal cortical dysplasia. Septum pellucidum was absent in both cases. The cortical dysplasia in case 2 corresponded to the same hemispheric location with the right schizencephalic cleft in case 1. The combination of schizencephaly and focal cortical dysplasia in siblings or twins has not been previously reported.     

Bone marrow involvement in small cell lung cancer: Prognostic significance and correlation with hematological and biochemical parameters

The more metastatic sites and bone marrow metastasis in small cell lung cancer (SCLC), the worse the prognosis. Diagnosing the bone marrow invasion at the beginning of the therapy is important for determining of the prognosis and planning the treatment. Abnormalities of some blood parameters may help to estimate the extent of bone marrow invasion by cancer cells. In this retrospective review, the changes in routine laboratory tests that may indicate bone marrow invasion, the predictive values of these tests, and the prognostic importance of bone marrow invasion were evaluated in SCLC patients who were being followed up according to a protocol. One hundred and forty‐four patients with SCLC were enrolled in this study. Retrospectively, it was evaluated that 25 (17.4%) of the patients had bone marrow metastasis. According to univariate analysis, there was a significant difference between hemoglobin, white blood cell count, platelet count, lactate dehydrogenase, alkaline phosphatase and uric acid of the patients with and without bone marrow involvement. Among the biochemical parameters, the elevated LDH and AP had the highest sensitivity and specificity as indicators of bone marrow invasion (0.80–0.82 and 0.84–0.78, respectively). The median overall survival of extensive‐stage disease with and without bone marrow metastasis were 4.0 ± 1.0 months (95% CI 2.2–5.7) and 7.0 ± 1.2 months (95% CI 4.7–9.3), respectively (P = 0.03). Bone marrow metastasis was found to be an indicator of a bad prognosis. Bone marrow biopsy, that is an invasive procedure, can be performed on selected patients who have changes of routine laboratory tests suggesting bone marrow invasion.     

The effects of the incision types in myringoplasty operations on cosmesis

There is no study based on objective measurements about the cosmetic results of myringoplasty operation in medical literature. This study aims to show the differences in the auriculomastoid angle between the operations which were done with postauricular and endaural incisions. The auriculomastoid angle of 20 patients having had postauricular myringoplasty operation were measured both preoperative and postoperative periods. The auriculomastoid angles of 17 patients having had endaural myringoplasty operation were also measured in both preoperative and postoperative periods. Also, the patients were asked whether there was a change in the shape of their ears. It was observed that the increase of the auriculomastoid angles of the patients who had myringoplasty by postauricular incision was statistically significant when compared to the ones having had the operation by endaural incision. Also, the patients who had myringoplasty operation by postauricular incision realized the change in their ears significantly when compared to the other group. In this study, esthetically better results were observed in the myringoplasty operations done by endaural incision than the ones done by postauricular incision. When deciding on the incision type, this should be considered.     

A Rare Complication of Adjustable Gastric Banding:Wernicke's Encephalopathy

Background:Wernicke'sencephalopathy is an uncommon complication seen after morbid obesity surgery. Neurological and cardiac symptoms can occur. Early and adequate replacement of thiamin is crucial. Methods: A patient, who was operated by adjustable silicone gastric banding had severe vomiting 1 week after the operation. Physical examination showed no abnormalities except neurological signs consisting of ataxia, disorientation and diplopia. All radiological and biochemical parameters were in the normal range. Result: After replacement of vitamin B₁ (thiamin) intravenously 20 mg twice daily, all the neurological signs regressed day by day. Oral thiamin pills have been continued. Conclusion: Wernicke's encephalopathy which occurs as a result of thiamin deficiency is a rare complication that has serious morbidity with rapidly progressing neurologic symptoms, and must be treated immediately. Surgeons who treat morbidly obese patients must follow the metabolic and nutritional status of the patient.     

Is Helicobacter pylori related to endothelial dysfunction during childhood?

Background: Helicobacter pylori infection has been proposed to have a role in the development of atherosclerosis preceded by endothelial dysfunction. The aim of the present study was to determine if a relationship exists between H. pylori infection in childhood and endothelial dysfunction and level of high‐sensitivity C‐reactive protein (hsCRP). Methods: Between October 2003 and November 2004, 28 subjects who were anti‐H. pylori IgG‐positive and 25 who were anti‐H. pylori IgG‐negative were included in the study. Mean ages of the H. pylori‐positive and negative groups were not significantly different. Endothelial functions were evaluated on Doppler ultrasonography of the brachial artery. Percent ratio of the change in systolic diameter during hyperemic phase to the basal diameter was evaluated. Each subject’s serum was tested for hsCRP, homocysteine and lipids. Results: Percent ratio of the change in systolic diameters during hyperemic phase to the basal diameter was not significantly different between the H. pylori‐negative and ‐positive groups (P > 0.29). Mean levels of hsCRP were also not significantly different (1.48 ± 1.8 g/dL vs 2.35 ± 3.33 g/dL; P > 0.24). Similarly, serum levels of lipids and homocysteine were not significantly different (P > 0.05 for all lipids). Conclusions: Non‐invasive techniques used in the present study were not indicative of early findings of atherosclerosis in H. pylori infection during childhood. Further studies are required to evaluate the relationship between early endothelial dysfunction and H. pylori infection in children with cardiovascular risk factors.