Clinicopathological features of cytokeratin 5-positive pulmonary adenocarcinoma.

Cytokeratin 5 (CK5) is a marker for pulmonary squamous cell carcinoma; however, CK5 is sometimes present in pulmonary adenocarcinoma (ADC), and there is insufficient information regarding the clinicopathological features of CK5-positive ADC. We aimed to explore the clinicopathological characteristics of CK5-positive ADC using immunohistochemistry. We prepared the following two cohorts: a resected cohort containing 220 resected tumours for primarily studying the detailed morphological characteristics, and a tissue microarray (TMA) cohort containing 337 samples for investigating the associations of CK5 expression with other protein expressions, genetic and prognostic findings. CK5-positive ADC was defined to have ≥ 10% tumour cells and presence of CK5-positive tumour cells in the resected and TMA cohorts, respectively. CK5-positive ADCs were identified in 91 (16.3%) patients in the combined cohort. CK5-positive ADCs had male predominance (P = 0.012), smoking history (P = 0.001), higher stage (P < 0.001), histological high-grade components (P < 0.001), vascular invasion (P < 0.001), mucinous differentiation (P < 0.001), spread through airspaces (P < 0.001), EGFR wild-type (P < 0.001), KRAS mutations (P < 0.001), ALK rearrangement (P < 0.001) and ROS1 rearrangement (P = 0.002). In the resected cohort, more than half the CK5-positive ADCs (19 cases, 65.5%) showed mucinous differentiation; the remaining cases harboured high-grade components. In the TMA cohort, CK5-positive ADCs correlated with TTF-1 negativity (P = 0.002) and MUC5B, MUC5AC and HNF4alpha positivity (P < 0.001, 0.048, < 0.001). Further, CK5-positive ADCs had significantly lower disease-free and overall survival rates than CK5-negative ADCs (P < 0.001 for each). Additionally, multivariate analysis revealed that CK5 expression was an independent poor prognostic factor. CK5-positive ADCs showed aggressive clinical behaviour, with high-grade morphology and mucinous differentiation.

The effect of tandospirone, a serotonin(1A) agonist, on memory function in schizophrenia.

BACKGROUND: The purpose of this study was to test the hypothesis that the addition of tandospirone, a 5-HT(1A) partial agonist, to ongoing treatment with typical antipsychotic drugs, would improve memory function in patients with schizophrenia. METHODS: Eleven outpatients (male/female = 7/4) with schizophrenia who had been on stable doses of haloperidol and biperiden were given tandospirone, 30 mg/day, for 4 weeks. The Wechsler Memory Scale-Revised (WMS-R) was administered at baseline and 4 weeks after the addition of tandospirone. The Brief Psychiatric Rating Scale (BPRS; Total, Positive, and Negative subscale scores) and the Simpson-Angus Scale for Extrapyramidal Symptoms (SAS) were also completed on the two occasions. To exclude the possibility of a practice effect on the WMS-R test, 11 age-matched patients with schizophrenia (M/F = 7/4) were tested at baseline and after a 4-week interval. RESULTS: Repeated measures analysis of variance revealed a significant time by group (patients with or without tandospirone) effect for the Verbal-, but not the Visual Memory composite scores of the WMS-R test; no significant change was observed in patients without tandospirone, whereas improvement in the Verbal Memory score was noted in patients receiving tandospirone. Moreover, there was improvement in the Inclusion score, an index of memory organization as measured by the Logical Memory subtest of WMS-R, only in patients with tandospirone. Scores on the BPRS and SAS were improved during treatment with tandospirone, but the effects did not reach statistical significance. CONCLUSIONS: The results suggest that adjunctive treatment with 5-HT(1A) agonists may improve some types of memory function in schizophrenia.

Effect of dipotassium clorazepate on amygdaloid-kindling and comparison between amygdaloid- and hippocampal-kindled seizures in rats.

We examined the effect of dipotassium clorazepate (7-chloro-1, 3-dihydro-2-oxo-5-phenyl-1H-1, 4-benzodiazepine-3-carboxylate potassium hydroxide), an antianxiety drug, on amygdaloid kindling and compared its effects for 7 successive days on amygdaloid- versus hippocampal-kindled seizures, using the rat kindling model of epilepsy. Dipotassium clorazepate at 5 mg/kg significantly delayed amygdaloid kindling. The contralateral cortical after-discharge duration in the dipotassium clorazepate-treated group was significantly shorter than the after-discharge duration in the amygdala in the first seven stimulations, whereas it was significantly shorter only in the first three stimulations in the control group, indicating that dipotassium clorazepate suppressed the spread of seizure activity from focus to contralateral cortex. Dipotassium clorazepate suppressed amygdaloid-kindled seizures at 2 and 5 mg/kg, while 1 mg/kg or more suppressed hippocampal-kindled seizures. Thus, differences in effective dosages in both amygdaloid- and hippocampal-kindled seizures may suggest a difference in the neuronal mechanisms involved in this kindling.

Effect of ceruletide on plasma monoamine metabolites in the rabbit.

Ceruletide, a cholecystokinin octapeptide-like substance, has been shown to have some effect on tardive dyskinesia. We, too, previously examined the effect of ceruletide on various types of involuntary movement, and found that responders tended to have high plasma homovanillic acid (HVA) levels. It is generally accepted that both central and peripheral sources make a contribution of plasma HVA. In this study, the response of plasma HVA in rabbits to ceruletide was investigated after pretreatment with debrisoquin sulfate, a drug which selectively blocks peripheral HVA production by inhibition of MAO. As a result, 8 and 50 micrograms/kg ceruletide treatment showed a tendency to decrease plasma HVA levels, but showed no significant differences; however, 140 and 200 micrograms/kg ceruletide showed a significant reduction of plasma HVA. These results are important to the understanding of the mechanism of ceruletide's effect on the brain, as well as to predict the effect of ceruletide on involuntary movements.

Semantic structure in schizophrenia as assessed by the category fluency test: effect of verbal intelligence and age of onset.

It has been reported that long-term memory function, including the semantic structure of category, is impaired in patients with schizophrenia. The present study was performed to determine: (1) whether the deficit in semantic structure in schizophrenia is independent of cultural backgrounds, and (2) the effect of age of onset and verbal intelligence on the degradation of semantic structure in these patients. Fifty-seven Japanese patients with schizophrenia and 33 normal control subjects entered the study. The semantic structure was derived by Multidimensional Scaling (MDS) analysis based on data from the ANIMAL category fluency test. The semantic structure was compared between: (1) schizophrenic patients as a whole vs. normal control subjects; (2) earlier onset (age of onset <20 years) vs. later-onset groups of patients; and (3) high Vocabulary score (score of the Vocabulary subtest from the WAIS-R>7) vs. low Vocabulary score patient groups. Normal control subjects demonstrated the domestic/size dimension in semantic structure, while no such dimension was obtained in patients with schizophrenia. The subgroup comparisons revealed that the later onset or the high Vocabulary score group maintained a relatively intact semantic structure compared with the earlier onset or the low Vocabulary score group, respectively. These findings suggest that the deficit in semantic structure in patients with schizophrenia is commonly observed irrespective of cultural backgrounds, and that age of onset and the level of verbal intelligence are closely related to severity of degradation of the semantic structure in schizophrenia.

A case of myasthenia gravis accompanied by invasive thymoma, alopecia areata and dry mouth.

We report a 43-year-old man suffering from myasthenia gravis with invasive thymoma accompanied with alopecia areata and dry mouth. These complications are extremely rare and the pathogenetic etiology of these complications was thought to depend on a generalized immunological disturbance.

Developments of the new instruments for TMJ arthroscopic surgery.

A large and clearly visible operating area is essential for successful arthroscopic surgery of the temporomandibular joint. The keys to a successful operation are the safe and accurate positioning of a large scope and multiple cannulations, overcoming blind areas. We developed some instruments to resolve these problems; i.e., scopes with a large diameter for high resolution, a triangulation instrument for multiple cannulations, a needle set-up jig for disk traction suture, a step cannulation system and a two-channel cannula for operating in the narrow lower joint space and a fixing jig for cannulas in the upper and lower joint space to observe the same portion of the discal tissue from both joint space during disk suturing. From our experience in applying systematic procedures using these instruments in 37 arthroscopic surgeries, it is possible for this procedure to be done under a visual field and the surgical time considerably shortened.

[Peripheral nerve disease associated with acute renal failure due to bromate poisoning].

A case of 21 year old male with neuropathy caused by renal insufficiency was present. He had taken bromate (mixed powder of potassium bromate and sodium bromate) for the purpose of suicide and suffered from acute renal insufficiency and hard of hearing. Renal dysfunction improved gradually by peritoneal dialysis and hemodialysis. However, on the 32th day after the onset, burning pain appeared in the bilateral feets. Following this, he began to complain of the disturbances of superficial and deep sensory below the ankle jerks and the weakness of his toes. Considering the clinical features, we supposed that the disturbance of the peripheral nerve was caused by uremia due to taking bromate. N. suralis was biopsied on the 80th day after the onset and examined electron microscopically. Electroscopical findings was as follows. Degeneration of the Schwann cells and irregularity or destruction of the myelin sheaths were observed. The axoplasm of the myelinated nerve fiber were relatively preserved as compared with the changes of the myelin sheaths. In the unmyelinated nerve fibers, cavity formations were observed. The findings of regeneration were not observed. From the electron microscopical findings, we speculate that the changes of the Schwann cells and the myelin sheaths are primary resulting from the disturbance of the metabolism of the Schwann cells. We speculate that anemia and hypoproteinemia caused by bromate disturbed regeneration.

[Histopathological findings of the nerve and muscles in familial primary amyloidosis, with special reference to the mechanism of amyloid fibril production].

T. I., a male aged 38, had a hereditary primary amyloidosis over four generation in his family history. He had peripheral neuropathy with dissociated sensory disturbances in the lower limbs, impotence, gastrointerstial dysfunction and orthostatic hypotention. N. suralis and M. quadriceps femoralis taken from him were examined by light and electron microscopy. N. suralis contained a lot of amyloids reacting with congo-red in the nerve fibres. Amyloid fibrils were remarkably observed around the blood vessels. They were continuous with the basement membrane of the endotherial cells. A few deposites were observed around the Schwann cell and fibroblasts. In M. quadriceps femoralis, amyloid like fibrils were noted in the perivascular spaces. Especially, a great deal of amyloid fibrils were continuous with the basement membranes. From this finding, it might be speculated that the basement membrane may play an important role in the production of amyloid fibrils.

[Long-term follow-up study on sequelae of carbon monoxide poisoning; serial investigation 33 years after poisoning].

1. We examined 156 patients 33 years after CO poisoning occurred at the Miike Mikawa Mine, Fukuoka, Japan. The subjects were classified according to age as follows: between 55 and 59 years (n = 14), 60 and 69 years (n = 62), 70 and 79 years (n = 60), and 80 and 87 years (n = 18). The mean age was 69.2 years old. Concerning the duration of coma that occurred soon after the accident, 64 remained comatose from 0 to 6 hours, 46 from 6 to 12 hours and 46 from 12 to 48 hours. 2. Subjective symptoms were observed in 96.8% of the patients. Among them, forgetfulness was noted in 89.7%, followed by irritability in 66.7%, headache in 59.6%, insomnia in 55.8%, limb pain in 46.8%, dull head feeling in 42.9% and dizziness in 36.5%. 3. Intellectual disturbances were observed in 68.6% of the patients, including impression disturbance in 58.3%, memory disturbance in 51.9%, calculation disturbance in 63.5%, thinking disturbance in 61.5% and disorientation in 14.1%. 4. Apathy and disorder of volition and interest which were found in 72.4% were included in personality change because all symptoms persisted for many years. Personality change was classified as follows: weakness of emotion and will (hypobulia) in 54.4%, infantilism in 35.2%, hyperactive, talkactive and lack of inhibition in 18.5%, lack of self-possession and unstable temper in 9.6%, depression in 15.3%, neurosis in 7.6% and schizophrenic state in 2.5%. Among these symptoms of personality change, weakness of emotion and will and infantilism were conspicuous among the patients who remained in a coma for more than 6 hours soon after the accident but showed no relationship with age. 5. Neurological symptoms that were found in 48.7% of the patients were classified as sensory disturbance in 25.6%, peripheral nerve symptoms in 16.0%, pyramidal symptoms in 14.1%, ataxia and cranial nerve symptoms in 7.1%, paroxysmal symptoms in 6.4% and focal symptoms in 4.5%, extrapyramidal symptoms in 21.8% (Parkinsonism in 4.5%, tremor in 10.9% and muscle rigidity in 16.0%) and vegetative symptoms in 37.2%. 6. At the time of investigation, 5 CO poisoning patients were classified as serious cases (3.2%), 20 as comparatively serious (12.8%) medium-degree cases, 28 as comparatively mild (17.9%) medium-degree cases, 37 as comparatively serious (23.7%) mild cases, 42 as comparatively mild (26.9%) mild cases, 24 (15.4%) as having symptoms which were not problematic, and 24 (15.4%) as having symptoms that markedly worsened due to complication. 7. A total of 138 (88.4%) cases had complications were classified as follows: 78 cases (50.0%) of hypertension, 62 cases (39.7%) of cerebral infarction, 24 cases (15.4%) of cardiac disturbance, 21 cases (13.5%) of diabetes mellitus, 14 cases (9.0%) of hepatic disturbance and six cases of silicosis (3.8%). 8. Cranial MRI was carried out for 129 cases (82.7%). Of the abnormal findings identified, cerebral atrophy accounted for 72.0% (93 cases), including moderate and severe cases in 47.2% (61 cases), pallidum lesion for 37.9% (49 cases), lacunar infarction (including cerebral infarction) for 52.7% (68 cases), and hippocampal atrophy for 18.6% (24 cases). Many cases of cerebral atrophy and hippocampal atrophy were observed in patients who remained in the initial coma for more than 12 hours and were 80 years of age or old. The cases of pallidum lesion were observed in patients who remained in the initial coma for more than 6 hours, and no relationship with age was found. The other findings, cerebral atrophy and lacunar infarction showed a slight relationship with age. 9. Among the moderate and serious cases of intellectual disturbance, cerebral atrophy constituted to 62.5%, lacunar infarction 68.7% and pallidum lesion 50.0%. Among the moderate and serious cases of personality change, cerebral atrophy constituted 78.5%, lacunar infarction 35.0% and pallidum lesion 50.0%. Moreover, among extrapyramidal symptoms, pallidum lesion constituted 58.6%, cerebral atrophy 55.1% and lacun

Massive immature teratoma in a neonate.

Teratomas are embryonal tumours composed of diverse tissues from three germinal layers with variable levels of maturity. The authors report a female patient with a large immature epignathus. Prenatal diagnosis permitted a caesarean section and tracheotomy to be planned under ex utero intrapartum treatment for airway obstruction. The tumour was successfully controlled, even though it was impossible to distinguish from normal tissue because it lacked a pedicle and capsule, using multidisciplinary therapy, including a series of surgical treatments and adjuvant chemotherapy. This case suggested that the level of serum alpha fetoprotein might be a useful indicator after surgery. At present, after 4 years, no regrowth has been observed and the patient has no problems with respiration or swallowing.

Pathological changes of peripheral nerve and muscle of patients with hemiatrophy.

Peripheral nerve and muscle of patients with hemiatrophy were biopsied and examined by means of light and electron microscope. The unmyelinated nerve fibers decreased in number and remaining fibers were atrophic with irregular shape and high electron density, while myelinated nerve fibers slightly decreased in number. The Schwann cells enveloping nerve fibers were also atrophic with high electron density. The muscles contained numerous glycogen granules in the myofilaments and between the myofilaments. The mitochondria in the muscles showed atrophy with high electron density. Some parts of severe atrophy showed honeycomb-like structure forming large vacuoles in the muscle fibers. From the findings mentioned above, it is speculated that primary change was nerve fibers, especially unmyelinated nerve fibers.

Electron microscopic study of experimental thallotoxicosis.

To adult male rats 2 mg per rat of thallium acetate: CH3 COOT1 was given orally daily for six months. Clinically, the experimental rats revealed only alopecia and showed no neurological signs. Pathological findings were noted in muscle and cerebrum. Marked changes were observed in muscles and were as follows: swelling and vacuolation of mitochondria, destruction of cristae, ruptures of mitochondrial membranes, degeneration of sarcoplasmic reticulum and destruction of myofilaments. In the cerebrum, there were vacuolation of mitochondria, dilatation of Golgi cisterns in hypothalamus and thalamus. Sciatic nerve, liver and kidney were intact. From this, we consider that T1+ ions selectively affect the muscle and its mitochondria.