Measurements of active and passive force of horizontal muscles in strabismus

A precision device was developed for quantitative measurement of the active and passive forces of the horizontal muscles in several different types of strabismus. The device consists of a tension gauge for measuring isometric muscle tension (active force) and passive length-tension (passive force), and a circular-motion guide mechanism. In normal subjects, the active force showed nearly linear changes with the eye position, as was reported in past studies. A similar relationship between the active force and the eye position was observed also in strabismus patients in our study. Normal subjects showed a stronger force in the medial than the lateral rectus muscle. Among strabismus patients, those with normal retinal correspondence (NRC)-intermittent exotropia showed a force closest to that of the normal controls. However, the force of the lateral rectus muscle was significantly greater in those with constant exotropia than in the normal controls. The active force of the medial rectus muscle was significantly smaller in those with dual retinal correspondence (DRC)-intermittent exotropia and constant exotropia. Conversely, the active force of the medial rectus muscle was significantly greater in those with esotropia, compared with the normal group. As for the passive force, there was no significant difference between the temporal passive force and the nasal passive force in the normal and esotropic groups, but the temporal passive force was significantly greater in the esotropic group. The magnitude of the force was greater in both directions when traction was applied against the muscle having the stronger active force. These results suggest that the lateral rectus muscle force is relatively stronger in patients with DRC-intermittent exotropia due to a weakness of the medial rectus muscle force, and that the absolute strength of the lateral rectus muscle force is increased in patients with constant exotropia, but in NRC-intermittent exotropia the muscle forces are almost normal. Those with esotropia are considered to have an absolute increase in the medial rectus muscle force.     

Movement-related cortical potential in patients with cerebellar dentate degeneration]

We reported movement-related cortical potentials (MRCPs) in 11 patients with lesion of the dentate nucleus (Machado-Joseph disease (MJD) 7 cases, dentato-rubro-pallido-luysian atrophy (DRPLA)1, myoclonus epilepsy associated with ragged-red fibers (MERRF)1, dyssynergia cerebellaris myoclonica (DCM) 2), and compared with those of 7 cases of multiple system atrophy (MSA) who were postulated to have mild dentate lesions (striato-nigral degeneration 2 cases, Shy-Drager syndrome 2, sporadic olivo-ponto-cerebellar atrophy 3), and 7 control subjects without any neurological findings. Further we classified the diseases into the following two groups based on the lesion of the dentate nucleus. One was MJD group that had normal or slightly abnormal electroencephalogram (EEG), and the other was DN group (DRPLA, MERRF, DCM) that had markedly abnormal EEG. One of the main findings from this study was smaller slope of the Ns' in the MJD and DN group and normal slope of BP. There was no significant difference in the slope of Ns' between MJD patients and DN patients. This result shows EEG abnormalities have no influence on MRCP recordings. These results suggest that Ns' component may reflect the function in the cerebellar dentate nucleus, and that MRCP is a useful diagnostic method in patients with cerebellar ataxia.     

Suppression of in vitro hemopoiesis by the monocytes in a patient with aplastic anemia associated with hepatitis]

The cause of aplastic anemia associated with hepatitis (AAH) is as yet still unknown. There is a supposed relation to the immune mechanisms, however few reports have shown the effects of monocytes on the pathogenesis in the patients with AAH. We have reported a case of a 12-year-old boy with AAH related to cytomegaloviruses, and studied the hemopoietic progenitors. He showed pancytopenia and hypoplasia of the bone marrow on admission to our hospital. The culture studies showed that mononuclear cells (MNC) of the bone marrow produced few hemopoietic colonies in all cell lineages. However, the depletion of adherent cells from the MNC increased numbers of erythroid, neutrophil-macrophage and megakaryocyte colonies. Furthermore, the addition of adherent cells of the peripheral blood suppressed the colony formation in the aforementioned cell lineages by marrow MNC from which adherent cells, phagocytic cells and T-cells were abrogated. The results way suggest that monocytes play some soles in the pathogenesis of aplasia through inhibitor of hemopoiesis.     

β2-glycoprotein I, anti-β2-glycoprotein I, and fibrinolysis

β₂-glycoprotein-I (β₂GPI) is a phospholipid-binding plasma protein that consists of five homologous domains. Domain V is distinguished from others by bearing a positively charged lysine cluster and hydrophobic extra C-terminal loop. β₂GPI has been known as a natural anticoagulant regulator. β₂GPI exerts anticoagulant activity by inhibition of phospholipid-dependent coagulation reactions such as prothrombinase, tenase, and factor XII activation. It also binds factor XI and inhibits its activation. On the other hand, β₂GPI inhibits anticoagulant activity of activated protein C. According to the data from knockout mice, β₂GPI may contribute to thrombin generation in vivo. Phospholipid-bound β₂GPI is one of the major target antigens for antiphospholipid antibodies present in patients with antiphospholipid syndrome (APS). Binding of pathogenic anti-β₂GPI antibodies increases the affinity of β₂GPI to the cell surface and disrupts the coagulation/fibrinolysis balance on the cell surface. These pathogenic antibodies activate endothelial cells via signal transduction events in the presence of β₂GPI. Impaired fibrinolysis has been reported in patients with APS. Using a newly developed chromogenic assay, we demonstrated lower activity of intrinsic fibrinolysis in euglobulin fractions from APS patients. Addition of monoclonal anti-β₂GPI antibodies with β₂GPI also decreased fibrinolytic activity in this assay system. β₂GPI is proteolytically cleaved by plasmin in domain V (nicked β₂GPI) and becomes unable to bind to phospholipids, reducing antigenicity against antiphospholipid antibodies. This cleavage occurs in patients with increased fibrinolysis turnover. Nicked β₂GPI binds to plasminogen and suppresses plasmin generation in the presence of fibrin, plasminogen, and tissue plasminogen activator (tPA). Thus, nicked β₂GPI plays a role in the extrinsic fibrinolysis via a negative feedback pathway loop.     

Fluctuations in Tumor Blood Flow under Normotension and the Effect of Angiotensin II-induced Hypertension

To elucidate the significance of angiotensin II (AID-induced hypertension chemotherapy, changes of tissue blood flow both in normal subcutis and in tumors (AH109A, LY80) were measured with the hydrogen gas clearance method. A newly-developed anesthetic machine was used to keep the animals' condition constant. Tissue blood flow in normal subcutis and tumors always fluctuated with time under normotension. The nature and the rate of fluctuation in tumor Wood flow were almost identical in two different types of tumors. However, the fluctuation of blood flow in tumor and that in normal subcutis were almost always inversely related when blood flows in these different tissues were measured simultaneously, i.e., when tissue blood flow in normal subcutis decreased, tumor blood flow increased, and vice versa. The findings supported the idea that the connection mode between the tumor vascular bed and normal vascular bed is a parallel circuit. Vascular resistance in the normal vascular bed under All-induced hypertension seemed to be greater than that under normotension, because the All-increased tumor blood flow always exceeded the maximum tumor blood flow under normotension. Due to the fluctuations of tumor blood flow, no-flow or low-flow areas, resistant to delivery of anti-cancer drugs, moved sporadically within the tumor under the normotensive condition. However, good conditions for drug delivery to tumor tissue were induced by All-induced hypertension.     

Case of dermatomyositis complicated with massive pleural effusion that preceded the myopathy]

A 36-year-old man was admitted to a hospital with complaints of fever, polyarthralgia and dyspnea. Erythema was observed on his face, extensor surface of the fingers and extremities, and a chest X-ray revealed massive bilateral pleural effusion. He had no sign of myopathy at this point. Pleural fluid was proved to be exudative and contained extremely high levels of hyaluronic acid. He was also complicated with interstitial pneumonitis and was given a pulse therapy with methyl prednisolone followed by daily administration of 55 mg prednisolone (PSL). Twenty days after the commencement of the therapy, pleural effusion decreased but muscle weakness gradually appeared, accompanied by elevation of myogenic enzymes. Myogenic changes on electromyogram, and irregularity of the muscle fibers with slight inflammatory cell infiltrates in a biopsy specimen were demonstrated. He was transferred to our hospital, and a diagnosis of dermatomyositis was made. Later, pleural effusion waxed and waned depending on the dosage of PSL, but no other causative disorder was demonstrated by extensive examinations. This case indicates that the pleuritis could be one of the vasculitic manifestations of dermatomyositis.     

Effusion cytology in aged patients with malignancy

During the last 10 years, 162 aged cases (60 yrs. to 96 yrs., average 75.7 yrs.) that had positive effusion cytology were confirmed to have malignancy on autopsy. The effusion cytology of samples from aged patients made the first clinical diagnosis of malignancy in 46% of the cases studied, and this frequency increased with increasing age. The effusion cytology results from aged patients with malignancy were observed to have the following characteristic pathology profiles; (a). In pleural effusion: The primary organ of cancer was mostly the lung. However the histological cell types varied from predominantly adenocarcinoma to small cell carcinomas, squamous cell carcinomas etc. (b). In ascitic effusion: The primary organ of cancer varied and included the stomach, gallbladder, pancreas and ovaries. In these cases, however, the histological cell type was predominantly adenocarcinoma.