Raman spectroscopy as an alternative rapid microbial bioburden test method for continuous, automated detection of contamination in biopharmaceutical drug substance manufacturing.

Aims: To investigate an in-line Raman method capable of detecting accidental microbial contamination in pharmaceutical vessels, such as bioreactors producing monoclonal antibodies via cell culture.

Methods And Results: The Raman method consists of a multivariate model built from Raman spectra collected in-line during reduced-scale bioreactor batches producing a monoclonal antibody, as well as a reduced-scale process with intentional spiking of representative compendial method microorganisms (n = 4). The orthogonal partial least squares regression discriminant analysis model (OPLS-DA) area under the curve (AUC), specificity and sensitivity were 0.

Microtubule dynamics influence the retrograde biased motility of kinesin-4 motor teams in neuronal dendrites.

Microtubules establish the directionality of intracellular transport by kinesins and dynein through polarized assembly, but it remains unclear how directed transport occurs along microtubules organized with mixed polarity. We investigated the ability of the plus end-directed kinesin-4 motor KIF21B to navigate mixed polarity microtubules in mammalian dendrites. Reconstitution assays with recombinant KIF21B and engineered microtubule bundles or extracted neuronal cytoskeletons indicate that nucleotide-independent microtubule-binding regions of KIF21B modulate microtubule dynamics and promote directional switching on antiparallel microtubules.

Cega: a single particle segmentation algorithm to identify moving particles in a noisy system.

Improvements to particle tracking algorithms are required to effectively analyze the motility of biological molecules in complex or noisy systems. A typical single particle tracking (SPT) algorithm detects particle coordinates for trajectory assembly. However, particle detection filters fail for data sets with low signal-to-noise levels.

Common general anesthetic propofol impairs kinesin processivity.

Propofol is the most widely used i.v. general anesthetic to induce and maintain anesthesia.

MR vs CT in progressive supranuclear palsy.

Nine progressive supranuclear palsy (PSP) patients were studied with computerized tomography (CT) and magnetic resonance (MR) in order to determine the efficacy of each in detecting atrophy of the brainstem. Three additional PSP patients were evaluated with MRI for quantitative (electronic) measurements of the colliculi, pons and midbrain tegmentum. Both CT and MRI were equally effective in demonstrating midbrain atrophy.

CT brainstem abnormalities in the differential diagnosis of Huntington's disease.

Thin-section computed tomographic (CT) scans of 1.5 mm thickness were obtained in the study of 44 consecutive patients with Huntington's disease (HD) and six patients with sporadic progressive chorea and dementia. Mild to moderate midbrain and pontine atrophy, a dilated third ventricle, and enlarged quadrigeminal plate cisterns were observed in most cases suggesting that brainstem atrophy is common in HD.

Palatal myoclonus associated with extremity tremor.

Palatal myoclonus associated with extremity movements such as myoclonus or tremor is uncommon and reports are rare. Five patients with palatal myoclonus and a rest tremor are presented. In four patients, a slow rest tremor (3 Hz or less) was present.

Tremor in progressive supranuclear palsy.

Reports of tremor in progressive supranuclear palsy (PSP) have been infrequent; some authors indicate that tremor is never seen in PSP. Five patients with PSP and tremor are presented. Our series of cases and those reviewed in the literature suggest that tremor occurs in 12-16% of PSP cases.

Primidone/phenobarbital-induced periodic alternating nystagmus.

A 37-year-old man with a history of seizures developed periodic alternating nystagmus (PAN) along with other signs of primidone/phenobarbital toxicity. The PAN gradually diminished in cycle length and intensity, finally resolving with gradual discontinuation of the drugs.

Downbeat nystagmus secondary to multiple sclerosis.

Downbeat nystagmus has been associated with an increasing number of neurologic disorders, yet, it has only rarely been described in multiple sclerosis. Two patients with downbeat nystagmus secondary to multiple sclerosis are presented. In one, the nystagmus cleared completely in three weeks.

Thin-section CT of midbrain abnormalities in progressive supranuclear palsy.

Thin-section computed tomographic (CT) scans of 3 and 1.5 mm thickness were obtained using the Philips Tomoscan 310 and General Electric 8800 CT/T scanners in the study of 10 consecutive patients with progressive supranuclear palsy (PSP) and 31 patients with other diseases. Marked midbrain and moderate pontine atrophy, a dilated third ventricle, and enlarged quadrigeminal plate cisterns were observed in all PSP cases.

Myorhythmia: a widespread movement disorder. Clinicopathological correlations.

The clinical manifestations of 24 cases and the autopsy findings of 6 cases of extremity myorhythmia are presented. Extremity myorhythmia is that form of myorhythmia in which rhythmic alternating movements predominantly involve the limbs. The main difference between the tremor of extremity myorhythmia and the tremor of parkinsonism is the slower tremor rate, 2 to 3 cycles/s in myorhythmia and 4 to 6 cycles/s in parkinsonism.

Ocular dipping.

In ocular dipping, a slow downward motion of the eyes is followed by a delay at the extreme of downgaze and terminated by a quick return to midposition. A 53-year-old man developed ocular dipping following prolonged hypotension. In contrast to previously described cases, we were unable to observe a delay phase in some cycles of dipping.

Cerebral mucormycosis (Phycomycosis) in a heroin addict.

Cerebral mucormycosis was found at autopsy in a 27-year-old male narcotic addict with rapidly progressive focal neurologic signs. There was no evidence of rhinocerebral involvement of systemic illness, and a nuclide brain scan suggested brain abscess.

The evolution of a brain abscess the complementary roles of radionuclide (RN) and computed tomography (CT) scans.

Serial Tc-99m glucoheptonate brain scans demonstrated a brain abscess in a patient from the earliest phase of acute focal encephalitis (cerebritis) through the capsule formation and the recovery phase. The role of the RN and CT scans in the diagnosis of the early stage of cerebritis and the complementary nature of RN and CT scans in intracranial infections, particularly abscesses, are discussed. Guidelines for the use of RN and CT scans are suggested.

Periodic alternating ping-pong gaze.

A patient had periodic alternating Ping-Pong gaze and massive bilateral ischemic cerebral infarction proved at autopsy. In previous cases, bilateral hemisphere involvement appears to have been common in most cases. Eye movements in Ping-Pong gaze are similar to the slow-eye movements seen in sleep, anesthesia, and other obtunded states, a result of disinhibition of inherent rhythms in the oculovestibular system.