Loss of RMI2 Increases Genome Instability and Causes a Bloom-Like Syndrome.

Bloom syndrome is a recessive human genetic disorder with features of genome instability, growth deficiency and predisposition to cancer. The only known causative gene is the BLM helicase that is a member of a protein complex along with topoisomerase III alpha, RMI1 and 2, which maintains replication fork stability and dissolves double Holliday junctions to prevent genome instability. Here we report the identification of a second gene, RMI2, that is deleted in affected siblings with Bloom-like features. Cells from homozygous individuals exhibit elevated rates of sister chromatid exchange, anaphase DNA bridges and micronuclei. Similar genome and chromosome instability phenotypes are observed in independently derived RMI2 knockout cells. In both patient and knockout cell lines reduced localisation of BLM to ultra fine DNA bridges and FANCD2 at foci linking bridges are observed. Overall, loss of RMI2 produces a partially active BLM complex with mild features of Bloom syndrome.

Ab initio calculation of the cross sections for electron impact vibrational excitation of CO via the (2)Π shape resonance.

The stabilization method is used to calculate the complex potential energy curve of the (2)Π state of CO(-) as a function of bond length, with the refinement that separate potentials are determined for p-wave and d-wave attachment and detachment of the excess electron. Using the resulting complex potentials, absolute vibrational excitation cross sections are calculated as a function of electron energy and scattering angle. The calculated cross sections agree well with experiment.

Verbal memory abilities of children with brain tumors.

Several critical neuroanatomical structures and pathways for memory performance are located in the third ventricle region. This led us to predict that verbal memory abilities would be more impaired in children treated for third ventricle tumors compared to those treated for cerebellar tumors. Archival data was obtained from 24 pediatric patients with third ventricle region tumors and 18 pediatric patients with cerebellar tumors. Neuroradiological verifications of tumor involvement and hydrocephalus severity (i.e., Evans Index) on preoperative scans and MRIs proximal to the time of the neuropsychological evaluation were conducted. The potential confounds of hydrocephalus severity, seizure medication, age, radiation treatment, and chemotherapy were addressed. Verbal IQ was comparable between tumor groups and in the Average range. The third ventricle region group performed significantly worse on list learning and delayed list recall compared to the cerebellar group. Their mean performance was in the clinically impaired range on both trials. The third ventricle region tumor group performed better than the cerebellar tumor group on Digit Span, a basic repetition, attention span task. These findings support the hypothesis that pediatric patients with third ventricle region brain tumors are more likely to be impaired on verbal recall tasks compared to pediatric patients with cerebellar brain tumors. In contrast, patients who were treated for cerebellar tumors were more impaired on the basic repetition, attention span task compared to patients who were treated for third ventricle tumors. Future studies should examine the specific neuroanatomical structures and pathways that are damaged and may influence differential cognitive impairments in children.

Carcinoma of the skin with perineural invasion.

PURPOSE: To evaluate the outcome and patterns of relapse in patients treated for skin carcinoma of the head and neck with either microscopic or clinical perineural invasion. METHODS AND MATERIALS: Radiotherapy alone or combined with surgery was used to treat 135 patients with microscopic or clinical evidence of perineural invasion of skin carcinoma. All patients had at least 2 years of follow-up. RESULTS: The 5-year local control rates without salvage therapy were 87% with microscopic perineural invasion and 55% with clinical perineural invasion. Overall, 88% of the local failures occurred in patients with positive margins. Almost half of the recurrences in patients with microscopic perineural invasion were limited to the first-echelon regional nodes. However, only 1 of 11 patients with basal cell carcinoma with microscopic perineural invasion had a nodal failure. Ninety percent of recurrences in patients with clinical perineural invasion occurred at the primary site. Cranial nerve deficits rarely improved after successful treatment of the primary disease. Radiographic abnormalities remained stable 30% of the time when patients had clinical evidence of progressive disease. CONCLUSIONS: Radiotherapy in patients with skin cancer with clinical perineural invasion should include treatment of the first-echelon regional lymphatics. The risk of regional node involvement is also relatively high for patients with squamous cell carcinoma with microscopic perineural invasion. In patients with clinical perineural invasion, the poor local control rates with conventional radiotherapy suggest a need for dose escalation with or without concomitant chemotherapy.

MR imaging of the trigeminal ganglion, nerve, and the perineural vascular plexus: normal appearance and variants with correlation to cadaver specimens.

BACKGROUND AND PURPOSE: MR imaging is the method of choice for evaluating the trigeminal nerve. Detection of abnormalities such as perineural tumor spread requires detailed knowledge of the normal MR appearance of the trigeminal nerve and surrounding structures. The purpose of this study was to clarify the normal MR appearance and variations of the trigeminal ganglion, maxillary nerve (V2), and mandibular nerve (V3) with their corresponding perineural vascular plexus. METHOD: S: MR images obtained in 32 patients without symptoms referable to the trigeminal nerve were retrospectively reviewed. The trigeminal ganglion in Meckel's cave, V2 within the foramen rotundum, and V3 at the level of foramen ovale were assessed for visualization and enhancement. The configuration of the perineural vascular plexus was recorded. Correlation to cadaver specimens was made. RESULTS: The trigeminal ganglion and V3 were observed to enhance in 3-4% of patients unilaterally. V2 and V3 were well visualized 93% of the time. The perineural vascular plexus of V2 was observed 91% of the time, and that of V3 in 97% of instances. CONCLUSION: This study characterizes the normal MR appearance of the trigeminal ganglion and its proximal branches. The trigeminal ganglion, V2, and, V3 are almost always reliably seen on thin-section MR studies of the skull base. Enhancement of the perivascular plexus is routinely seen; however, enhancement of the trigeminal ganglion, V2, or V3 alone is seen only on occasion as supported by the avascular appearance of these anatomic structures in cadaver specimens.

Peripheral third cranial nerve enhancement in multiple sclerosis.

Cranial nerve III dysfunction in multiple sclerosis (MS) is uncommon. Seven cases of isolated cranial nerve III paresis associated with MS have been reported in the English-language literature. MR imaging was obtained in five cases demonstrating lesions within the midbrain. We present the detailed clinical and MR imaging findings of a young woman with MS and an isolated, painful pupil involving complete left cranial nerve III palsy. Initial MR imaging showed isolated enhancement of the cisternal portion of the cranial nerve III, suggesting that peripheral nervous system involvement may develop as part of the disease process in some patients with MS.

Carcinoma of the skin of the head and neck with perineural invasion.

BACKGROUND: Perineural invasion is observed in a small subset of patients with carcinomas of the skin of the head and neck. METHODS: Review of the patient literature highlighting the University of Florida experience. RESULTS: Patients with early perineural invasion are asymptomatic, and the phenomenon is discovered only on pathologic examination of the excised lesion. These patients are defined as having "incidental" perineural invasion, and treatment with surgery followed by postoperative irradiation results in a cure rate of approximately 80%. Undiagnosed, the perineural carcinoma slowly progresses and eventually results in symptoms, usually facial weakness or numbness. The disease eventually extends to the skull base and becomes incompletely resectable. Symptomatic patients are defined as having "clinical" perineural invasion, and aggressive treatment results in a cure rate of approximately 45%. CONCLUSIONS: Perineural invasion is an uncommon spread pattern observed in patients with skin cancer and is associated with a relatively poor prognosis. The likelihood of cure is inversely related to the proximal extent of the cancer and is lower for symptomatic compared with asymptomatic patients.