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A 56-year-old man experienced dyspnea since August 1995 and the chest X-ray film showed abnormal shadow. The diagnosis of bronchiolitis obliterans organizing pneumonia (BOOP) was established based on the histological findings of transbronchial lung biopsy. The patient was treated with prednisolone and symptoms improved. Myalgia and muscle weakness developed associated with relapse of BOOP after withdrawal of prednisolone. Patient was admitted to our department on December 1995 for further examination. An increased level of serum CPK, histological findings of muscle biopsy consistent with myositis, and positive anti-Jo-1 antibody were identified. Those findings supported a diagnosis of polymyositis (PM), and BOOP was considered as a pulmonary complication of PM. Myositis and pulmonary lesion improved after second course of steroid therapy and patient was discharged on May 1996. Both chronic pulmonary fibrosis and acute progressive interstital pneumonia are well known as pulmonary lesion associated with PM. The former is frequently recognized in cases of PM with anti-Jo-1 antibody and the latter is often observed in cases without autoantibodies. The association of PM and BOOP, however, has rarely been reported. The findings that BOOP frequently preceded PM and anti-Jo-1 antibody was positive in half of the cases were observed in the literature.

In order to clarify the flow dynamics of cerebrospinal fluid (CSF) in normal pressure hydrocephalus (NPH), a phase-contrast cine magnetic resonance (MR) imaging technique with retrospective cardiac gating was used to measure the quantitative flow velocity of CSF in the aqueduct in patients with NPH after subarachnoid hemorrhage (SAH-NPH group, n = 17), idiopathic NPH (1-NPH group, n = 2), asymptomatic ventricular dilatation or brain atrophy (VD group, n = 7) and healthy volunteers (control group, n = 19). Intracranial pressure (ICP) and pressure volume response (PVR) were also measured during the shunt operation in six of the SAH- NPH group. The maximum CSF flow velocity (Vmax) in the aqueduct was significantly larger in the SAH-NPH group (9.21 +/- 4.12 cm/sec, mean +/- SD) than in the control group (5.27 +/- 1.77, p < 0.001) and the VD group (4.06 +/- 1.81, p < 0.005). Vmax was not different between the control and VD groups. There was a positive correlation between the PVR and the peak CSF flow velocity in the SAH-NPH group. These findings suggest that the changes of CSF flow velocity in the SAH-NPH group might be caused by a moderate decrease of intracranial compliance. The CSF flow study using MRI is useful to differentiate NPH from brain atrophy or asymptomatic ventricular dilatation and also to estimate the intracranial compliance.

In order to clarify the pathogenesis of hypercalcemia in multiple myeloma, we measured plasma levels of parathyroid hormone related peptide (PTHrP), tumor necrosis factor alpha (TNF-alpha), tumor necrosis factor beta (TNF-beta), intact PTH and, serum 1,25-dihydroxyvitamin D in fifteen patients of multiple myeloma. We also measured serum levels of inorganic phosphorus (iP) and alkalinephosphatase activity (ALP). No significant differences in iP (3.2 +/- 0.4 vs. 4.0 +/- 2.2 mg/dl), ALP (150 +/- 28 vs. 335 +/- 305 IU/l) 1,25(OH)2 D (31.5 +/- 17.0 vs. 23.3 +/- 11.2 pg/ml) or TNF-alpha (7.8 +/- 2.1 vs. 8.0 +/- 2.0 pg/ml) were observed between normocalcemic and hypercalcemic patients. Plasma iPTH levels in hypercalcemic patients were significantly lower than those in normocalcemic patients (28.5 +/- 9.4 vs. 16.3 +/- 5.6 pg/ml, p = 0.01). Plasma levels of TNF-beta were less than 15.6 pg/ml in all subjects. On the other hand, the frequency of patients with abnormally high plasma levels of PTHrP was significantly greater (2/9 for normocalcemia vs 5/6 for hypercalcemia, chi 2 = 5.20, p = 0.02) in patients with hypercalcemia than in normocalcemic patients. Furthermore, a significant positive relationship between plasma PTHrP levels and corrected serum calcium levels (cCa) was observed using Spearman's correlation analysis by rank in fifteen myeloma cases (rs = 0.66, p = 0.013). These results suggest that PTHrP might be involved in the elevation of serum calcium levels in hypercalcemic myeloma patients. However, a few cases exhibit normocalcemia despite elevated plasma PTHrP levels or hypercalcemia without high plasma PTHrP levels. Therefore, further studies are necessary to elucidate the pathogenesis of hypercalcemia in multiple myeloma.

A 67-year-old woman presented with a 1-year history of gradual weight loss, reduced mental activity, muscle weakness, and urinary dysfunction. Neurological examination revealed mild lethargy, severe muscular atrophy, and diminished deep tendon reflexes in the extremities. The levels of vitamin B1 and folate in blood were low: 1.9 micrograms/dl (normal range 2.0-7.2) and 0.7 ng/ml (normal range 4.0-12.0). respectively. A lumbar puncture was done. The pressure of the cerebrospinal fluid was within normal limits, the level of protein was very high (467 mg/dl), and only a few lymphocytes were seen. A nerve-conduction study showed low amplitudes of action potentials and slow conduction velocities in both the motor and sensory nerves. Myelin irregularity, "onion bulb formation", and axonal atrophy were seen in a specimen obtained by sural nerve biopsy. A T2-weighted magnetic resonance image of the brain showed ventricular dilatation, high-intensity signals around the lateral ventricles, and a flow-void sign of the cerebral aqueduct. Radioisotope cisternography (111In-DTPA) disclosed ventricular reflux and slow clearance of the tracer from the ventricles. These findings indicated the presence of chronic inflammatory demyelinating polyneuropathy, nutritional polyneuropathy, vitamin B1 deficiency, folate deficiency, and normal pressure hydrocephalus. In this patient, the high level of protein in the cerebrospinal fluid may have caused the hydrocephalus.

A 76-year-old woman was found to have acute aseptic meningoencephalitis with meningial irritation, disturbance of consciousness, elevation of cell counts in cerebrospinal fluid, and swelling of a right temporal-lobe lesion on a CT scan of the head. Muscle weakness in the lower extremities and urinary dysfunction developed and progressed gradually. The protein content of cerebrospinal fluid was high, and the distal latencies of F waves were prolonged, which suggested that the inflammation extended to the nerve roots. Sjögren's syndrome was diagnosed on the basis of atrophy of the labial salivary glands; invasions of lymphocytes and plasma cells to the intercellular space; and elevation of the titers of serum antinuclear antibody, anti-SS-A antibody, and anti-SS-B antibody. The patient had no xerosis. Aseptic meningoencephalitis was the first manifestation of Sjögren's syndrome. In recent years, several cases in which Sjögren's syndrome was associated with aseptic meningitis have been reported. However, we know of no previous report of such a case in a patient of this age. Aseptic meningoencephalitis can be the first manifestation of Sjögren's syndrome.

Lipoprotein(a) (Lp(a)) is an independent risk factor for cardiovascular diseases in non-diabetic people, but few studies have been done in diabetic patients. To investigate whether Lp(a) is a risk factor for cardiovascular disease in elderly people with diabetes, we examined the association of Lp(a) and serum lipid levels (total cholesterol: TC; triglycerides: TG; and high-density lipoprotein cholesterol: HDL-c) with the incidence of coronary artery disease and cerebrovascular disease. We studied 354 outpatients(131 men and 223 women, 60-97 years of age) with non-insulin-dependent diabetes mellitus. The mean concentration of Lp(a) was 21.1 +/- 19.6 mg/dl and the median was 14.0 mg/dl. The Lp(a) concentration did not correlate significantly with age or with sex, but it did correlate significantly with TC (r = 0.152, p < 0.05) and with the level of apoprotein B (r = 0.168, p < 0.05). The incidence of cerebrovascular disease was significantly higher in patients with high concentrations of Lp(a) (> or = 30 mg/ dl) than in those with low concentrations (< 30 mg/ dl). Multivariate logistic regression analysis revealed that male sex, hypertension, a high level of HbA1c, a low level of HDL, and a high level of Lp(a) were independent risk factors for cerebrovascular disease. The incidence of coronary artery disease tended to the higher in those with high concentrations of Lp(a) (> or = 30 mg/dl). However, multivariate logistic regression analysis revealed no significant correlation between Lp(a) concentration and the incidence of coronary artery disease. We conclude that a high concentration of Lp(a) is an independent risk factor for cerebrovascular disease in elderly patients with diabetes.

Turbo spin-echo magnetic resonance (MR) imaging of a patient with hemifacial spasm clearly demonstrated vascular compression of the facial nerve by the vertebral artery. The high resolution images of this method may be an appropriate alternative to preoperative cerebral angiography. Turbo spin-echo MR imaging is a diagnostic procedure of choice for patients with hemifacial spasm and possibly trigeminal neuralgia.

Recently, various cDNA sequences coding protein-tyrosine phosphatases (PTPs) have been reported and their extensive similarities in the catalytic domains clarified, but knowledge of the structures and organizations of their genes is still limited. In this study, a detailed structure and organization of the human intracellular LC-PTP (also called HePTP) gene is reported. The 13 to 18.5 kb genomic clones encoding human LC-PTP have been isolated. The LC-PTP gene is organized into 11 exons, including the 5'-noncoding first exon and the 3'-noncoding exon. Splicing sites for exons 4 to 10, which encode the conserved catalytic PTP domain, arise almost at the same position as for the CD45 gene. This elucidation of the LC-PTP gene structure provides insight into the domain evolution of intracellular LC-PTP and transmembrane CD45, which may be generated by gene duplications of an ancestral gene.

Cisplatin in combination with vindesine has been widely used for the treatment of advanced non-small-cell lung cancer (NSCLC), producing an overall response rate of 32%. We conducted a phase II study to examine whether the addition of carboplatin to the combination of cisplatin and vindesine would improve the antitumor activity of the two platinum agents in advanced NSCLC without increasing their toxicity. Carboplatin (240 mg/m2) and vindesine (3 mg/m2) were given intravenously on day 1 and cisplatin (60 mg/m2) and vindesine (3 mg/m2), on day 8. Of the 40 evaluable patients with advanced NSCLC, 12 showed a partial response, for an overall response rate of 30% (95% confidence interval, 17%-47%). The median duration of response was 12 weeks, and the median survival duration for all patients was 38 weeks. The major toxicity was hematologic: leukopenia (WHO grade > or = 3) was observed in 21 patients (53%) and anemia (WHO grade > or = 3), in 13 patients (33%). However, thrombocytopenia was mild and WHO grade 3 toxicity was observed in only 4 patients (10%). Nonhematologic toxicities consisted mainly of WHO grade > or = 2 nausea and vomiting in 16 patients (40%) and WHO grade > or = 2 alopecia in 11 patients (28%). No significant nephrotoxicity or neurotoxicity was seen. Our findings indicate that the addition of carboplatin to the combination of cisplatin and vindesine does not improve antitumor activity in patients with advanced NSCLC.

Protein-tyrosine phosphorylation and dephosphorylation are directly associated with cellular growth, signal transduction, and neoplastic transformation. Here we report the isolation of a complementary DNA (cDNA) clone encoding a novel protein-tyrosine phosphatase (PTP) from a human T cell PEER cDNA library. The predicted open reading frame encodes a approximately 68-kDa protein composed of 593 amino acids which contains two src-homology region 2's (SH2 domains) at the N terminus; this PTP is designated as SH-PTP3. Northern blot analysis revealed that SH-PTP3 mRNA was expressed throughout many tissues and the transcriptional size was consistent at about 6.0 kb. As with other SH2 domains in src-family kinases, the SH2 domains of SH-PTP3 may play a crucial role in interactions with tyrosine phosphorylated signaling proteins, including itself and protein tyrosine kinases (PTKs), to regulate targets' enzyme activity.

We studied the effect of the depletion of glutathione on the synthesis of proteoglycan and collagen in cultured chick chondrocytes. When the cultured chondrocytes were incubated with 1 mM buthionine sulfoximine (BSO), a specific inhibitor of gamma-glutamyl-cysteine synthetase, the intracellular glutathione level markedly dropped within 12 h with no loss of cell viability. Incorporation of 35SO2-4 into proteoglycan was lowered in the presence of BSO. When the 35S-labeled proteoglycans were separated into two fractions by glycerol density gradient centrifugation, the inhibitory effect of BSO on the synthesis of proteoglycan was greater in the fast-sedimenting proteoglycan fraction, which consisted mainly of cartilage specific large proteoglycan (PG-H), than in the slowly sedimenting proteoglycan fraction. The inhibition by BSO of the synthesis of core protein-free glycosaminoglycan chains primed by p-nitrophenyl-beta-D-xyloside was smaller than the inhibition of the synthesis of proteoglycan. Analysis of glycosaminoglycans labeled with [3H]glucosamine indicated that the treatment of chondrocytes with BSO resulted in a small increase in the proportion of synthesis of hyaluronic acid to the synthesis of total glycosaminoglycan. The incorporation of [3H]proline into collagen was also inhibited by BSO. Sodium dodecyl sulfate polyacrylamide gel electrophoresis of the 3H-labeled collagen showed that, in the presence of BSO, processing of Type II collagen appeared to slow down and the proportion of Type X collagen synthesis was reduced.

In Mycobacterium avium complex strains, which were not exposed previously to any antituberculosis drugs, resistances to rifampin, minocycline, and kitasamycin, and resistances to streptomycin and kanamycin appeared frequently in the same strains. These data indicate that patterns of drug resistance in these organisms are not random but occur through linked mechanisms.

We prospectively studied serum antiviral antibody response in adult patients with febrile upper respiratory tract infections. Paired sera were obtained in 158 patients from January 1982 to December 1983. Eighteen patients (11.4 percent) showed a significant antibody rise in the convalescent phase of the disease compared to the acute phase. Significant antibody rise was observed against all viruses examined: influenza viruses type A and B, adenovirus type 3, respiratory syncytial virus, and parainfluenza viruses type 1, 2 and 3. Two patients responded simultaneously to two viruses. Serum interferon was detected in acute phase of the disease in 4 of 8 patients examined in whom viral infections were proved. Detected interferon was alpha type.

A survey was carried out on the biological and biochemical characteristics of 661 strains of Mycobacterium avium-M. intracellulare complex that caused lung disease in the period 1976 to 1986. The results showed that the proportion of strains which showed 2-week-arylsulphatase activity and that of those which were able to utilize glucose as sole carbon source in the presence of glutamate-nitrogen decreased markedly, and that the proportion of those which utilized neither n-butanol nor iso-butanol as sole carbon sources in the presence of ammoniacal nitrogen increased markedly over these 11 years. These findings indicate that the predominant biotype changed from M. intracellulare to M. avium during the period under study. This postulate is supported by a limited study of the serovars present among the isolates.

The rate of sputum conversion (continuously negative cultures for six months or more) was compared among four regimens given to 83 patients with moderately advanced, cavitary lung disease caused by Mycobacterium avium complex untreated previously. The regimens of rifampin + isoniazid + enviomycin and rifampin + isoniazid + streptomycin appeared to be superior to the regimen of rifampin + isoniazid + ethambutol. No statistically significant difference was observed between the regimens rifampin + isoniazid + enviomycin and rifampin + isoniazid + streptomycin.

Forty-nine strains of Escherichia coli isolated from piglets with or without neonatal diarrhea were all negative for both classical heat-labile and heat-stable enterotoxins when examined by the 18-hour rabbit ileal loop test with culture supernatants, the mouse Y1 adrenal cell test, and the infant mouse test. Of them, seven strains from diarrhea were positive only when tested in porcine ileal loops challenged with living bacterial cell suspensions or culture supernatants. The enterotoxic component produced by them was resistant to heating at 80 degrees C for 20 minutes. It presented a rapid onset of action with a long duration, although the amount of accumulated fluid in the porcine ileal loops was small. These porcine strains of E. coli which has been positive only for the porcine ileal loop test were designated "ST pig loop" or "STpl" strains.