Computational design of mechanically coupled axle-rotor protein assemblies.

Natural molecular machines contain protein components that undergo motion relative to each other. Designing such mechanically constrained nanoscale protein architectures with internal degrees of freedom is an outstanding challenge for computational protein design. Here we explore the de novo construction of protein machinery from designed axle and rotor components with internal cyclic or dihedral symmetry. We find that the axle-rotor systems assemble in vitro and in vivo as designed. Using cryo-electron microscopy, we find that these systems populate conformationally variable relative orientations reflecting the symmetry of the coupled components and the computationally designed interface energy landscape. These mechanical systems with internal degrees of freedom are a step toward the design of genetically encodable nanomachines.

Aberrant expression of beta- and gamma-catenin is an independent prognostic marker in oral squamous cell carcinoma.

Alteration in expression of E-cadherin and catenins is associated with loss of differentiation, acquisition of an invasive phenotype and poor clinical outcome in many types of cancer. To identify molecular prognostic markers, membrane expression levels of E-cadherin, and alpha-, beta- and gamma-catenin in biopsy samples (n=135) of oral squamous cell carcinoma (OSCC) were evaluated immunohistochemically in relation to preoperative tumour-related features, clinical course and prognostic value, and were found to be significantly correlated with an endophytic growth pattern and pathologically proved lymph-node metastasis. Alteration of expression of E-cadherin, and alpha-, beta- and gamma-catenin was also significantly correlated with poor disease-specific 5-year survival (P=0.0096, 0.0434, 0.0005 and 0.0005, respectively). Multivariate Cox proportional hazard regression analysis showed that alteration of beta- and gamma-catenin expression was a significantly independent prognostic parameter for survival (P=0.0112 and 0.0088, respectively), as was the case with endophytic growth pattern and advanced N-category. These results indicate that patients with OSCC and absent or reduced membrane expression of beta- and gamma-catenin should be considered a high-risk group for regional lymph-node metastasis and poor prognosis.

Evaluation of fungal DNA sequence using polymerase chain reaction in infection-free vitreous humor.

We evaluated the vitreous bodies from 14 clinically nonfungal infectious eyes to establish a baseline for the presence of a fungal genome using polymerase chain reaction (PCR). The vitreous samples were all PCR negative, except for one eye with chronic uveitis. Blood samples examined were all PCR negative. We concluded that fungal DNA sequences could not be amplified in vitreous specimens obtained from patients with clinically diagnosed proliferative diabetic retinopathy, macular hole, or epiretinal membrane.

[Genetic diagnosis of aspergillosis].

Aspergillosis is an opportunistic infection caused by pathogenic Aspergillus species (spp.) and is a major hazard for immunocompromised patients and even for non-immunocompromised individuals. Clinical diagnosis of aspergillosis, especially invasive pulmonary aspergillosis (IPA) is difficult and is largely presumptive, typically based on spiking fevers not responding to antibiotics in a patient with the risk factors. It is well known that Aspergillus spp. can be only infrequently cultured from clinical specimens, and that the cultural examination is laborious and time-consuming. Moreover, positive culture from bronchoalveolar lavage or sputa is indicative, but not proof of infection. The criterion for diagnosis of pulmonary infection by aspergilli requires repeated isolation of the same species of Aspergillus from respiratory specimens. There have been some successful attempts using serological assays to detect circulating antibodies to Aspergillus spp. in the noninvasive form of the disease, but these are generally negative in an acute phase IPA patient. A currently available serodiagnostic kit, Pastrex Aspergillus is limited in clinical usefulness because of low sensitivity and specificity in spite of being simple and rapid. Contamination of clinical specimens with various saprophytic filamentous fungi other than aspergilli also often give false positive. Diagnostic methods using such molecular biological techniques, as polymerase chain reaction (PCR) have recently been employed to identify DNA from a number of pathogens when diagnostic means are limited. PCR is known as the most sensitive and specific technique by which to detect a specific DNA sequence. In this paper we have reviewed new genetic methods of diagnosing aspergillosis including PCR and in situ hybridization.

Dibutyryl cAMP inhibits endotoxin-induced increases in pulmonary vascular resistance and fluid filtration coefficient in the perfused rat lung.

We investigated the effects of pre-treatment with dibutyryl cAMP (db-cAMP) or cGMP on endotoxin-induced hemodynamic changes and pulmonary vascular permeability in isolated perfused rat lungs. Intraperitoneal injection of Salmonella enteritidis endotoxin (2 mg/kg) caused increases in pulmonary arterial resistance (Ra) after venous reservoir elevation, in pulmonary filtration coefficient (Kf) and in lung wet-to-dry (W/D) weight ratio. Pre-treatment with db-cAMP blocked endotoxin-induced increases in Ra, Kf and W/D weight ratio. Pre-treatment with cGMP attenuated only the increase in Ra caused by endotoxin. Moreover, administration of db-cAMP 2 hours after endotoxin injection attenuated the increase in Ra induced by endotoxin treatment. The increases in Kf and W/D weight ratio caused by endotoxin were not affected by post-treatment with db-cAMP. Since the increases in Ra, Kf and W/D weight ratio caused by endotoxin were blocked by pre-treatment with db-cAMP, agents that increase intracellular cAMP level may be useful to prevent acute pulmonary vascular injury.

Comparison of muscle force, muscle endurance, and electromyogram activity during an expedition at high altitude.

Handgrip force (HF), maximal pinch force (MF), muscle endurance (ME), and the median power frequency (MdPF) of the activity shown in the electromyogram (EMG) were studied at various altitudes in eight normal healthy subjects. MF and ME were measured between the index finger and thumb, and all measurements were obtained at altitudes ranging from 610 to 4860 m during an expedition in the Qinghai Plateau in China. With the change in altitude HF, ME, and MF showed no significant change. Compared to the MdPF at 2260 m on ascent, the MdPF at other altitudes showed a significant decrease (P < 0.01). Thus, we conclude that muscle performance (HF, MF, and ME) was not affected by the environment at high altitude. However, MdPF was affected and the mean MdPF at 610 m after the expedition did not recover to initial values of MdPF. We suggest these results may have been affected by fatigue and chronic exposure to the hypobaric hypoxic environment, since the members of the expedition party expressed feelings of sluggishness and fatigue after the expedition.

Primary hepatic marginal zone B-cell lymphoma with mantle cell lymphoma phenotype.

We report a rare case of primary hepatic lymphoma, Stage II disease, in a 48-year-old male who had a solitary hepatic tumour measuring 4 x 4.5 x 3 cm. The tumour showed a nodular growth pattern and lymphoepithelial lesions with bile ducts. Some neoplastic nodules had a non-neoplastic atrophic germinal centre and/or a thin mantle cell layer. Morphologically, the neoplastic cells were centrocyte-like cells or intermediate lymphocytes. They expressed L26(CD20)+/LN-1(CDw75)+/-/LN-2(CD74)+/cyclin D1- and had a monotypic immunoglobulin of cytoplasmic IgM (kappa) on paraffin sections. The neoplastic cells or neoplastic nodules expressed surface IgM+/surface IgD+/-/Leu-1(CD5)+/DRC-1+/alkaline phosphatase+/B1(CD20)+/B4(CD19)- on fresh frozen sections. We therefore diagnosed this case as primary hepatic marginal zone B-cell lymphoma with mantle cell lymphoma phenotype. We confirm that it is difficult to differentiate extranodal marginal zone B-cell lymphoma (low grade B-cell lymphoma of mucosa-associated lymphoid tissue type; MALT lymphoma) and mantle cell lymphoma.

Sound stimulation-induced vasomotor reflex in the central artery of the rabbit ear.

Effects of sound stimulation on the central artery of the rabbit ear were studied as a somato-autonomic reflex. Vasoconstriction and dilatation, caused by metronome sound stimulation, were estimated from the temperature fluctuations in the central artery of the ear, measured by a thermistor. To enhance the detection of temperature rises, moderately high background levels of arterial tone were established by exposing the tips of the ears to water at a temperature of 10 degrees C or 5 degrees C, prior to sound stimulation. A fall in arterial temperature due to vasoconstriction was observed immediately after the start of the 1-min sound stimulation, with a subsequent temperature rise which overshot the original basal level due to vasodilatation. A positive correlation between the ear temperature before sound stimulation and the temperature fall (p < 0.01), and a negative correlation between the ear temperature and the temperature rise (p < 0.05) were obtained. The temperature fall was blocked by phenoxybenzamine (9 mg/kg, i.p., p < 0.01). The subsequent rise was not influenced by atropine (3 mg/kg, i.p.) or phenoxybenzamine, however, it was attenuated by hexamethonium (6 mg/kg, i.p., p < 0.05). The temperature fall at the beginning of sound stimulation was related to alpha-adrenergic mechanism. The subsequent temperature rise was thought to be related to parasympathetic mechanism, excluding cholinergic mechanism.

Influence of hypoxia and pulmonary air embolism on lung injury in perfused rat lungs.

We investigated the influence of low oxygen ventilation, air-bubble infusion into the pulmonary artery and their synergistic effect on pulmonary hemodynamics and microvascular permeability in isolated perfused rat lungs. Pulmonary arterial pressure was significantly increased by 70 min of ventilation with 3% O2 (hypoxia, group H); by 0.2-ml air-bubble infusion (pulmonary air embolism, group AE), and by 0.2-ml air-bubble infusion and 70 min of 3% O2 ventilation (hypoxia and pulmonary air embolism, group H & AE) compared with that of a control group (0.2 ml saline infusion, group C). Neither total (TPR) nor arterial (Ra) pulmonary vascular resistance in group H showed any difference compared to control values. TPR and Ra in groups AE and H & AE were significantly higher than those in group C. However, there was no significant difference in TPR or Ra between groups AE and H & AE. The pulmonary capillary fluid filtration coefficient, dry lung to wet lung weight ratio and white blood cell count in the perfusate of group H were not changed, while those of the groups AE and H & AE were significantly increased compared to those of controls. However, there was no significant difference in these values between groups AE and H & AE. Since hypoxia did not damage isolated perfused rat lungs, as determined by hemodynamics and permeability, nor enhance lung injury caused by air embolism, it was suggested that air embolism contributed more to high-altitude lung injury than low oxygen.

Food restriction inhibits an autoimmune disease resembling systemic lupus erythematosus in (NZB x NZW) F1 mice.

To investigate the beneficial effects of food restriction on systemic lupus erythematosus in NZB x NZW F1 mice, we separated the mice into three groups. One was fed a diet in which total food intake was reduced to 60% of normal from age 2 mo onward, while the animals were still healthy (group 2R). A second group was selected at age 7 mo based on a positive lupus nephritis (proteinuria) and fed the 40% restricted diet thereafter (group 7R); a third group was allowed to consume food ad libitum (control). All control mice died of renal disease by age 14 mo, whereas all mice in group 2R and 80% of those in group 7R were living at that age. Measurements of anti-double stranded DNA antibody concentrations in sera and in supernatants of in vitro spleen cell cultures revealed that the production of the immunoglobulin G, but not immunoglobulin M, class of antibodies was markedly and significantly reduced in food-restricted mice. Age-associated changes in lymphocyte subsets seen in control mice, i.e., increases in B:T and CD4:CD8 T cell ratios, decreases in NTA260+ T cell subsets, and increases in aberrant activated NTA204+CD4+ T cells and cycling cells, were all significantly lessened in underfed mice. Food restriction did not suppress the secondary acquired antibody responses to a foreign antigen. Thus, the beneficial effects of food restriction in these mice may be related to the lessening of the age-related onset of T cell subset abnormalities, including activation of autoreactive T cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of BQ123 on vasoconstriction as a result of either hypoxia or endothelin-1 in perfused rat lungs.

A possible role of endothelin (ET)-1 in mediating hypoxic pulmonary vasoconstriction (HPV) was examined by comparing haemodynamic differences between ET-1-induced vasoconstriction and HPV in isolated perfused rat lungs. An ETA receptor antagonist (BQ123) was also employed to assess the effects of ET-1. The pulmonary arterial pressure (Ppa) was significantly increased by alveolar hypoxia (3% O2) and by ET-1 (5 nM). The pulmonary microvascular pressure was not changed by hypoxia, but increased more than two-fold by ET-1 (P < 0.01). Hypoxia significantly increased pulmonary arterial resistance (P < 0.01) while ET-1 significantly increased pulmonary venous resistance (P < 0.01), and slightly increased arterial resistance. Lung weight was increased by ET-1 and decreased by hypoxia, accompanied by similar Ppa responses in both cases. BQ123 (10(-6) M and 10(-5) M) did not influence the changes in Ppa and lung weight induced by hypoxia or angiotensin II (0.3 micrograms). BQ123 did, however, suppress (P < 0.05) the increase in Ppa and lung weight induced by 5 nM ET-1. Thus, it appears unlikely that ET-1 is involved in changes in pulmonary vascular tone during acute HPV.

Functional CD4+ T cell subsets defined by expression of CD45RC and NTA260 antigens and age-associated polarization in murine lupus.

Using two mAb, one specific to the alternative exon 6-dependent epitope of CD45 molecules (JH6.2) and one a natural thymocytotoxic autoantibody (NTA) with an unknown reactive epitope (NTA260), we subdivided splenic CD4+ T cells from 2-month-old BALB/c mice into five phenotypically distinct subsets. CD45RC+NTA260- (S I) cells were phenotypically analogous to CD4+ T cells predominating in newborn mice and produced a significant amount of IL-2, but not so IL-4, IL-10 or IFN-gamma when stimulated with immobilized anti-CD3 mAb in vitro. They appeared to consist mainly of naive ThP cells. The CD45RC+NTA260+ (S II) subset also produced IL-2, but not other cytokines; however, the IL-2 levels produced were much higher than seen with the S I subset, thereby suggesting the predominance of further maturated ThP cells. The CD45RC-NTA260+ (S III) subset mainly produced IL-4, IL-10, IFN-gamma and less IL-2, and contained memory cells that helped the secondary antibody response to a recall antigen, and hence contained Th2 and probably a mixture of Th0 and Th1 cells. The CD45RC-NTA260- (S IV) subset was a poor responder to the immobilized anti-CD3 mAb. The CD45RCbrightNTA260dull (S V) subset consisted of a small number of cells that were phenotypically analogous to activated CD4+ T cells. While an age-associated decrease in the proportion of S I and less markedly in S II and in turn increase in S III subsets of CD4+ T cells occurred in normal BALB/c mice, autoimmune disease-prone (NZB x NZW)F1 mice showed a marked age-associated decrease in the proportion of not only S I, II but also III subsets. As aged (NZB x NZW)F1 mice carry CD4+ T helper cells for IgG anti-DNA antibody production, such age-associated polarization to the S IV subset appears to be critical in the pathogenesis of autoimmune disease in these mice.

[A 51-year-old man with early onset parkinsonism].

We report of 51-year-old man with early onset parkinsonism. The patient was well until 38 years of age, when he noted a difficulty in the use of his right leg; this difficulty improved after he received a medicine from his physician. He did not take medicine regularly, and he noted difficulty in standing up from a chair and in rolling over at age 40. Tremor was not a feature, but he noted slowness in his movements at age 42; at age 49, he noted diurnal fluctuation in his symptoms and at times he experienced hallucination. He was admitted to our hospital in September of 1992 for the first time when he was 50-year-old. At that time, neurologic examination revealed an alert and somewhat bradyphrenic man; Hasegawa dementia rating scale was 20/30. Cranial nerves were intact except for masked face and small voice. He showed stooped posture and small step gait cogwheel rigidity was noted in the four limbs more on the left; tremor was absent. Deep reflexes were within normal range and the sensation was intact. As he showed diurnal fluctuation in his symptoms, his medication was switched to levodopa 3,000 mg/day without a peripheral decarboxylase inhibitor. He was discharged for out patient follow up. But he did not take drugs regularly, and his neurologic condition deteriorated; he was admitted to another hospital. Neurologic examination at that time was essentially similar to that of his first admission to our hospital, except that he showed more severe rigidity and akinesia; again tremor was not detected. His cranial CT scan showed a mild ventricular dilatation without cortical or brain stem atrophy. During his hospital stay, he developed episodes of oculogyric crisis during peak dose of levodopa, and orthostatic hypotension. He developed pneumonia and expired on October 28, 1993. He was discussed in a neurological CPC, and the chief discussion arrived at the conclusion that the patient had early onset Parkinson's disease of Lewy body type. As differential diagnoses, early onset parkinsonism without Lewy body, pure form of diffuse Lewy body disease, pallidoluysian atrophy, and other conditions were considered; however, all of those possibilities were excluded. Early onset parkinsonism without Lewy body would have much earlier onset than this patient, and diffuse Lewy body disease would show more profound dementia 13 years after the onset. Pallidoluysian atrophy would be complicated with some dystonic features. Post-mortem examination showed marked discoloration and degeneration of the substantia nigra. The degeneration was most prominent in the ventrolateral tier of the substantia nigra.(ABSTRACT TRUNCATED AT 400 WORDS)

[A 65-year-old woman with dysarthria, dysphagia, weakness, and gait disturbance].

We report a 65-year-old woman with progressive dysarthria, dysphagia, weakness, and gait disturbance. The patient was well until 59 years of age (January of 1986) when she noted bilateral ptosis. One year later, she noted a gradual onset of difficulty in speech (articulation). Her speech slowly deteriorated and she noted weakness in chewing power and difficulty in swallowing in addition. In October 1987, she developed emotional incontinence. In January of 1988, she started to drag her left foot. She was admitted to our hospital on June 13 of 1988. On admission, she was alert and general physical examination was unremarkable. Neurologic examination revealed no dementia; her higher cerebral functions appeared intact. Ptosis was present bilaterally more on the right. She showed difficulty in opening her eyes on command; no contraction of the frontal muscles was seen upon attempted eye opening. There was a moderate limitation in the vertical gaze. Forced laughing and crying were seen. Facial muscles were moderately weak without apparent atrophy. The movement of the soft palate was very weak, and swallowing disturbance was more prominent for liquid staff. The tongue appeared somewhat small, however, no fasciculation was noted. Her step was small and the posture was stooped. Retropulsion was present, however, Romberg's sign was absent. No muscle atrophy was apparent, however, diffuse mile to moderate muscle weakness was noted in all four limbs. Cerebellar sign was absent. Deep tendon reflexes were exaggerated bilaterally, and Babinski sign was present on the left side. Sensation was intact. Routine blood tests were unremarkable as was a cranial CT scan. Her ptosis did not improve after 10 mg of edrophonium injection. CSF was also normal. She was transferred to another hospital but her neurological disabilities further progressed. In 1989, she was totally unable to move her limbs; she could only move her eyes; still consciousness was clear without dementia. She developed respiratory difficulty and expired on July 25, 1992. She was discussed in a neurological CPC, and the opinions were divided into ALS and primary lateral sclerosis (PLS). The chief discussant arrived at the conclusion that the patient might have had the pyramidal form of ALS. Postmorten examination revealed marked myelin pallor in the anterior as well as lateral corticospinal tracts. Pyramidal tract degeneration was prominent starting at the level of the cerebral peduncle and was continued to be seen until the level of lumbar cord. The number of anterior horn cells showed only slight decrease in the cervical level, however, it was normal in the lumbar cord.(ABSTRACT TRUNCATED AT 400 WORDS)

Cardiopulmonary function in bicycle racing over mountainous terrain at moderate altitude.

To examine cardiopulmonary function during exercise in a mountainous region at moderate altitude, we measured cardiac frequency, oxygen consumption (VO2), and percentage arterial hemoglobin oxygen saturation (%SaO2) before and after a bicycle race with a starting point at 638 m and finishing point at 1980 m. The time required to ascend an elevation of 10 m was prolonged with increasing altitude, and heart rate also increased with altitude. The %SaO2 at the starting point and at the finishing point differed significantly (P < 0.01). Faster cyclists exhibited higher %SaO2 and lower VO2, while slower cyclists exhibited a reduction in %SaO2 and an increase in VO2 immediately after the race. The %SaO2 recovery time was significantly correlated with the racing time (r = 0.54, P < 0.001). Therefore, the faster cyclists' oxygen debt upon completion of the race may be small and recovery of cardiopulmonary function may be fast, while the slower cyclists' oxygen debt may be large and recovery of cardiopulmonary function may be slow.

Cardio-pulmonary function of cyclists competing on an ascending mountain course between altitudes of 1400 m and 2800 m.

Physiological changes were investigated in the cardio-respiratory function of competitors in a bicycle race which involved not a flat course but ascending a mountain, from 1400 m to 2800 m. Heart rate throughout the race, arterial oxygen saturation and pulmonary function before and after the race of well trained competitors were measured. The individual's maximal heart rate during the race was designated as HRmax for the calculations. (1) There were significant correlations between the age and the mean %HRmax during the race, between mean %HRmax and time, and between age and time (n = 15); the mean %HRmax had a 3.90 times greater effect on time than did age. (2) The individuals who performed best had lower values of oxygen saturation just after finishing the race (n = 51). (3) At 1 min after reaching the finishing line, oxygen saturation levels had recovered to the value of 20 min after finishing the race, whereas the heart rate was still in the process of recovery (n = 18). (4) Maximum expiratory flow at 50% vital capacity measured 30 min after reaching the finishing line was significantly higher than at the starting point. The intensity of the load on the cardiac system produced by completion of this course was estimated to be almost the same as that of a full marathon on a flat course. The time depended on both the youth of the cyclist and on his ability to maintain a high value of %HRmax during the race.

Effect of dibutyryl cyclic AMP on morphologic features and marker production of human cervical argyrophil small-cell carcinoma cell line.

The effect of dibutyryl cyclic AMP (dB-cAMP) on the morphologic features and marker production of a human cervical argyrophil small-cell carcinoma (ASCC) cell line was examined. Following 1-5 days' exposure to 5 mM dB-cAMP, morphologic differentiation as defined by the expression of cytoplasmic processes (stellate cells) was observed. The number of stellate cells depended on the dose of dB-cAMP and incubation time. Shortly after removal of dB-cAMP from the culture medium, the treated cells returned to their original spherical shape. dB-cAMP caused a reduction in the growth rate of cells which recovered after removal of the agent. The morphological changes appeared not to be the result of growth inhibition by dB-cAMP, because the cells maintained in a serum-free medium did not show any change in shape. Electron microscopic study revealed the development of intracytoplasmic microtubules, microfilaments, and an increase in the number of neurosecretory granules in the treated cells. The levels of neuron-specific enolase, serotonin and gastrin in treated cells were significantly higher than those in untreated controls. These findings indicate that a reversible differentiation of cultured ASCC cells into neuroendocrine cells occurs in a growth medium containing dB-cAMP.

Effects of exercise training at 1,500 m on arterial oxygen saturation and pulse rate.

We compared the effects of exercise training at a low (610 m) altitude with those at moderate (1,500 m) altitude on arterial oxygen saturation (SaO2) and pulse rate (PR) between two groups of men: five subjects in the low altitude group (LG), and five other subjects in the moderate-altitude group (MG), after giving them a series of bicycle training in a hypobaric chamber. Training intensity was 75% HRmax for 60 min/day, 3 times per week for 5 weeks. Before and after the training, Sao2 and PR were measured with a pulse oximeter during step-tests under various air pressures, corresponding to 610 m, 2,000 m, and 4,000 m, respectively, in the chamber. We found that: 1) Sao2 during the step-test carried out at 2,000 m and 4,000 m in the hypobaric chamber was significantly increased in MG compared with that in LG; and 2) PR during the step-tests at 610 m, 2,000 m, and 4,000 m was significantly decreased in MG compared with that in LG. Thus, we conclude that exercise training at a moderate altitude is a useful method for increasing Sao2 and decreasing PR and may prevent mountain sickness.

Immunohistochemical study of cytokeratin 7 for the differential diagnosis of adenocarcinomas in the ovary.

Mucinous adenocarcinomas of the ovary were studied immunohistochemically for cytokeratins 7 and 18, either to determine whether the ovarian tumor was primary or a metastasis or to establish the histogenetic origin of the tumor. Primary ovarian tumors were strongly positive for both cytokeratins, while ovarian metastases from colonic cancers were negative for cytokeratin 7, as were the colonic cancers. Three of four ovarian tumors complicated by pseudomyxoma peritonei were negative for cytokeratin 7, indicating appendiceal origin. Two of seven mucinous tumors associated with dermoid cysts were negative for cytokeratin 7, suggesting gastrointestinal origin.

[A 47-year-old woman with meningeal signs and consciousness disturbance].

We report a 47-year-old woman with SLE, who developed meningeal signs and consciousness disturbance. She noted an onset of fever, and swelling and pain in her face, hands and feet in 1990. She was seen in another hospital and the diagnosis of SLE was made. She was treated with prednisolone with marked improvement in her symptoms. She was well with 5 mg of oral prednisolone daily until January of 1991, when she developed fever, myalgia and weakness in her legs. She was admitted to the medical service of our hospital on August 5. She was receiving 15 mg of prednisolone daily. Gram positive rods were cultured from her blood on August 5. She became incoherent 2 days later, and had a convulsive episode on August 8. After the convulsion, she lost consciousness from which she did not recover. Her CSF contained 304/3 microliters cells, 29 of which were neutrophils, 6 lymphocytes, 90 others, and 179 destructed cells. The CSF protein content was 345 mg/dl, and glucose 23 mg/dl. A neurological consultation was asked on August 9. Physical examination at that time revealed a semicomatous woman. Respiration was 30/min and regular. BP 132/82 mmHg, heart rate 122/min and regular, and BT 39.6 degrees C. General physical examination was unremarkable. Pertinent neurologic findings were positive Kernig sign and spasticity in all four limbs. Brain stem reflexes were retained. Upon painful stimulation, withdrawal response was elicited both lower extremities. She was treated with pipiracillin, latamoxef and phenobarbital, however, she had frequent seizures. She was deeply comatose on December 10. She became flaccid and no more meningeal signs were observed.(ABSTRACT TRUNCATED AT 250 WORDS)