A Chemical Probe for Dark Kinase STK17B Derives Its Potency and High Selectivity through a Unique P-Loop Conformation.

STK17B is a member of the death-associated protein kinase family and has been genetically linked to the development of diverse diseases. However, the role of STK17B in normal and disease pathology is poorly defined. Here, we present the discovery of thieno[3,2-d] pyrimidine SGC-STK17B-1 (11s), a high-quality chemical probe for this understudied "dark" kinase. 11s is an ATP-competitive inhibitor that showed remarkable selectivity over other kinases including the closely related STK17A. X-ray crystallography of 11s and related thieno[3,2-d]pyrimidines bound to STK17B revealed a unique P-loop conformation characterized by a salt bridge between R41 and the carboxylic acid of the inhibitor. Molecular dynamic simulations of STK17B revealed the flexibility of the P-loop and a wide range of R41 conformations available to the apo-protein. The isomeric thieno[2,3-d]pyrimidine SGC-STK17B-1N (19g) was identified as a negative control compound. The >100-fold lower activity of 19g on STK17B was attributed to the reduced basicity of its pyrimidine N1.

Pain in multiple leiomyomas alleviated by nifedipine.

We have confirmed the usefulness of nifedipine in the treatment of pain present in lesions of multiple skin leiomyomata. Our patient, a 28-year-old woman, had hundreds of skin lesions, proven histologically to be leiomyomata. Nifedipine (10 mg) three or four times daily was remarkably effective in diminishing pain that was more marked in the winter season.

Facial neurorrhaphy with autologous sural nerve graft using the CO2 laser in a primate model.

Cranial nerves, being of fine caliber and having a poorly defined epineurium, pose problems in intracranial sutural anastomosis. The CO2 laser is a comparatively new prospect that is being evaluated for sutureless neural anastomosis. Because there are no reports on the laser anastomosis of a peripheral spinal nerve to a cranial nerve, we designed this study to explore the possibility of performing a laser anastomosis of the facial nerve, using an autologous sural nerve graft in a primate model. Six monkeys underwent resection of the right facial nerve in the parotid fossa. In five of them, the CO2 laser was used to anastomose sural nerve interposition grafts by the use of microsurgical techniques. In one control animal, the sural nerve graft was interposed between the cut ends of the facial nerve and no anastomosis was performed. Compound muscle action potentials were recorded preoperatively and 2, 4, and 6 weeks postoperatively. At the end of 6 weeks, the wound was again explored and the grafts were examined. The neurophysiological results showed that in the five laser-welded nerves, at 4 weeks and 6 weeks postoperatively, the proximal latencies showed an improving trend with each successive recording. It was concluded that the CO2 laser can be used for the anastomosis of interposition grafts to the facial nerve.

Intraspinal mesenchymal chondrosarcoma. Case report.

A 52-year-old man presented with symptoms of progressive cervical radiculomyelopathy. A myelogram showed an intradural block at the C-6 level. Magnetic resonance T1-weighted imaging revealed a hypointense, sausage-shaped mass extending from C-3 to C-6, located posterolaterally on the right side and pushing the spinal cord to the left and anteriorly. At surgery, a mass was found attached solely to the pia mater, with a normal arachnoid and dura mater overlying it. The mass was excised completely and microscopic examination identified a mesenchymal chondrosarcoma. The patient was symptom-free 6 months after surgery.

Nondiagnostic CT-guided stereotactic biopsies in a series of 407 cases: influence of CT morphology and operator experience.

Nondiagnostic biopsies were analyzed in a consecutive series of 407 patients undergoing computerized tomography (CT)-guided stereotactic biopsies. These were categorized as either negative biopsies, when normal tissue or nonspecific pathology was found, or inconclusive, when a definitive diagnosis could not be made although representative tissue was obtained. Nineteen biopsies (4.7%) were negative and 10 (2.4%) were inconclusive, giving an overall nondiagnostic biopsy rate of 7.1% (29 of the 407 cases). Suspected neoplastic masses (390 cases) were classified on the basis of their CT morphology into four groups: Group 1 included purely hypodense nonenhancing masses; Group 2 included isodense nonenhancing masses; Group 3 included ring-enhancing masses; and Group 4 included mixed-density enhancing masses. Although a higher proportion of hypodense nonenhancing masses (six of 56, or 10.7%) yielded a negative result, there was no statistically significant difference in the negative biopsy rates for the different CT categories (p = 0.06). The negative biopsy rates for the 6 years of the study, 1987 to 1992 (1987 being an incomplete year) were as follows: 13.3%, 6%, 3.2%, 3%, 5.8%, and 2.7%. There was no significant decrease in the negative biopsy rate as experience with this procedure increased (p = 0.20). A total of eight surgeons independently performed the biopsies. There was no significant difference (p = 0.24) in the negative biopsy rate of the surgeon with the most experience (124 biopsies, 2.4% negative biopsy rate) compared with that of the seven other surgeons combined (283 biopsies; 5.7% negative biopsy rate). These findings suggest that the yield in a stereotactic biopsy is independent of the CT appearance of the mass. Adherence to certain basic principles in patient and target selection will ensure a reasonable percentage of positive yield with stereotactic biopsy procedures even if the surgeon is relatively inexperienced. There does not appear to be a learning curve in the performance of CT-guided stereotactic biopsies. The management of patients with nondiagnostic biopsies is discussed.

Histological studies in primary neuritic leprosy: changes in the apparently normal skin.

The visually normal skin of 196 patients diagnosed clinically to have primary neuritic leprosy was studied histologically to determine whether there were any specific changes due to the disease in this site. Histological changes due to leprosy were seen in 32.1% of the patients, and included, indeterminate leprosy in 19.4%, borderline tuberculoid leprosy in 6.6% and borderline lepromatous leprosy in 6.1%. The remaining biopsies showed mild non-specific dermal inflammation, mild nerve changes or no significant lesion. The nerve inflammation and/or granulomas were mostly in the deep dermal nerves or neurovascular complexes. This study shows that there is a cutaneous component to primary neuritic leprosy and the disease is not totally confined to nerves. The absence of visible hypopigmented patches in these patients is probably related to the deep location of the dermal inflammation.

Desmoplastic low grade astrocytoma: a case report and review of literature.

A 7-year-old girl presented with focal seizures without symptoms of raised intracranial tension. Routine histological, immunocytochemical and ultrastructural methods revealed a desmoplastic low grade cerebral astrocytoma. Follow up for 2 years after biopsy did not show recruitment of neurological symptoms or signs. Biphasic tumours containing glial and mesenchymal elements have been described in the literature under various diagnostic headings. As the histologically benign variants of mixed glial and mesenchymal tumours appear to have a good prognosis, identification of these as separate entities seems imperative. With a review of literature we propose a pathological classification of mixed glial and mesenchymal tumours.

Orbital apex leiomyoma with intracranial extension.

BACKGROUND: Leiomyoma is a rare, benign smooth muscle tumor of the orbit. It occasionally shows some histologic resemblance to other common tumors of the orbit like neurofibroma and schwannoma. Its location at the orbital apex is uncommon and only one case with intracranial extension has been reported so far. CASE DESCRIPTION: A nine-year-old boy presented to us with left orbital pain. Four years earlier he had undergone partial excision, elsewhere, of a tumor at the orbital apex, which was reported as a schwannoma. The computed tomography (CT) scan showed regrowth of the tumor with intracranial extension. The tumor was totally resected by an intracranial route. One year postoperatively there was no recurrence of the tumor. CONCLUSIONS: Leiomyoma of the orbit, though a benign tumor, does show regrowth after partial excision. Total excision, including any intracranial component, is advised. The cases reported so far are reviewed and the histopathology and possible etiopathogenesis of this tumor are discussed.

Quantitative analysis of CD1a (T6) positive Langerhans cells in human tonsil epithelium.

Fifty-one human palatine tonsils of both sexes and 4-54 years of age were studied for quantitative analysis of Langerhans cells in the epithelium using CD1a (T6), which is a specific immunological marker for Langerhans cells and indeterminate cells. Cryo-sections were stained using the avidin biotin peroxidase method. Using light microscopy, CD1a-positive dark brown cells with dendritic processes were identified as Langerhans cells, which were located in the epithelium, subepithelial tissue, follicles and interfollicular areas. The Langerhans cells were counted only in the tonsil epithelium per zone of 1.1 mm length of basement membrane. For each biopsy, 25 such zones were studied. The mean number (SEM) of Langerhans cells per zone of tonsil epithelium was found to be 37 (+/- 0.5). In the male, it was 36 (+/- 0.7) but in the female, it was 38 (+/- 0.2). In different age subgroups, the mean number (SEM) varied between 40 (+/- 1.7) and 14 (+/- 1.1). In the age subgroups of 11-15, 16-20, and 21-25 years, the mean number showed significant sex differences. Since the 11-15, 16-20, and 21-25 age subgroups in the female showed an increased number of Langerhans cells, it is concluded that the immunological role of the palatine tonsils is increased during puberty and adolescence. In the female, there was a negative correlation (r = -0.196, p < 0.01) between age subgroups and mean numbers, but in the male there was no correlation (r = 0.008). Overall, in all the 51 biopsies together, there was a negative correlation (r = -0.017, p < 0.01) and significant (p < 0.001) sex and age differences.

Cysticercosis of the flexor digitorum profundus muscle producing flexion deformity of the fingers.

Selective flexion deformity of the middle and ring fingers resembling a mild type of Volkmann's contracture resulted from Cysticercus cellulosa infection within the deep flexor muscle of the forearm in a middle-aged woman. Excision of the fibrotic segment of the muscle and tenodesis of all the flexor profundus tendons restored normal range of motion to these fingers. Vascular compromise in addition to the inflammatory response to the infection were considered causes for the deformity. There is no previous report of this kind in the literature.

Primary chondroid chordoma of the base of the petrous temporal bone.

The authors describe an unusual case of a primary chondroid chordoma arising from the base of petrous temporal bone. The patient, a young male, presented with a left sided jugular foramen syndrome. The CT findings of a tumour arising from the base of the left petrous temporal bone were confirmed at infratemporal exploration. The clinical and histopathological and immunohistochemical differences between classical (typical) chordoma and its chondroid variant are highlighted. The rarity of primary chordomas at this site is stressed.

Smear diagnosis of central nervous system lesions : a critical appraisal.

Smears, imprints and frozen sections have been recognised as useful adjuncts to diagnosis by the traditional paraffin section in neurosurgical biopsies. In this study, 251 intracranial space occupying lesions were studied by smears and paraffin sections to determine the causes of error and the possible means to avoid them. There were 63 computed tomography guided stereotactic microbiopsies and 188 open biopsies. The overall diagnostic accuracy was 88. In 6.8 of cases the tumour type was diagnosedcorrectly, but the grade was altered subsequent to examining the paraffin sections owing probably to sampling errors. Only 5.2 of cases had an entirely incorrect diagnosis.

Medullomyoblastoma: A case report.

Medullomyoblastoma is a rare tumour seen in childhood. We report a medullomyoblastoma occurring in the cerebellar vermis of a 4 year old boy. The light microscopic features, immunohistochemistry and histogenesis are described.

Subacute sclerosing panencephalitis : CT and MR imaging in a rapidly progressive case.

We report the findings on CT and MR imaging in a patient with rapidly progressive subacute sclerosing panencephalitis (SSPE), which correlated with the clinical progression of the disease. In view of the rapid neurological deterioration and CSF pleocytosis, a brain biopsy was done and this confirmed the diagnosis.

CT guided stereotactic surgery : an overview of 600 procedures.

The aim of this paper is to present our experience with CT guided stereotaxy, documenting the types of procedures performed and their outcome. Over the past five and a half years, 600 stereotactic procedures have been performed using the Brown Roberts Wells (BRW) stereotactic system. The procedures were categorized as (i) diagnostic biopsies : 431; (ii) Therapeutic procedures (Aspirations) : 52; (iii) functional procedures: 13; and (iv) stereotactic craniotomies: 104. False negative or nondiagnostic biopsies were obtained in 28 out of 431 diagnostic procedures (6.5 percent) and in 3 cases the procedure was terminated without taking a biopsy. Two of 483 patients undergoing stereotactic biopsy or aspiration died due to procedure related complications (0.41 percent). Seven patients had major morbidity associated with this procedure (1.44 percent) and 12 others had transient worsening of neurological status (2.48 percent). All functional procedures were done for movement disorders. Stereotactic craniotomies were performed for excision of small lesions in eloquent areas. Of 600 procedures, the preoperative objective was achieved in 564 cases (94 percent). Stereotactic surgery has very low mortality and morbidity and plays an important role in the management of intracranial lesions.

Melanotic neuroectodermal tumor of the epididymis. A case report.

Melanotic neuroectodermal tumors occur very rarely in the epididymis, only eleven cases having been reported to date in the world literature. An additional case is reported which we believe is the first from India.

Krukenberg tumor of ovary with features of mucinous cystadenocarcinoma.

An unusual case of bilateral Krukenberg tumors having a predominant multicystic mucinous component which on gross and microscopic examination resembled a mucinous cystadenocarcinoma is presented. It is important to distinguish between these two tumors as Krukenberg tumours have a significantly worse prognosis.

Malignant 'multinodular' oncocytoma of parotid gland--a case report and literature review.

The pathological findings in a multinodular malignant oncocytoma of the parotid gland in a male 62 years of age, with tumour infiltration into the adjacent skin and skeletal muscle and with regional lymph node metastasis is presented.

Transplant associated Kaposis sarcoma.

This case reports the first transplant associated Kaposis sarcoma reported from India.

Effects of intranasal challenge with group A beta haemolytic streptococcus M type 49 in Swiss albino mice.

Mice are susceptible to natural infections with streptococci and therefore can serve as suitable animal models to study experimental streptococcal infections. In an earlier study, we had shown the development of pharyngeal colonization, antibody response and histopathological changes in the heart following intranasal (IN) challenge with a rheumatogenic serotype of group A beta haemolytic streptococcus, the M type 18. To determine if nonpharyngitis associated serotypes can also elicit similar responses, 30 Swiss albino mice were challenged intranasally with 2 x 10(7) colony forming units of a skin associated serotype of group A beta haemolytic streptococcus, the M type 49. Pharyngeal colonization varied from 64% (n = 30) in the first week to 69% (n = 16) during the fourth week after IN challenge. Eleven (36.7%) of the 30 animals studied showed antibody response to DNase B (ADNB) with peak titers varying from 150 to 1200 units. Wide variations were seen in ADNB titers in individual mice. Histopathological evidence for cardiac lesions were seen in three animals. The changes were mild and varied from mild to chronic endocardial inflammation to calcification. The study shows that Swiss albino mice are also susceptible to IN challenge with skin associated strains of GABHS and therefore can serve as useful models to study the effects of experimental infection with diverse serotypes of GABHS.