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Chromosome 13 is the largest acrocentric human chromosome. It carries genes involved in cancer including the breast cancer type 2 (BRCA2) and retinoblastoma (RB1) genes, is frequently rearranged in B-cell chronic lymphocytic leukaemia, and contains the DAOA locus associated with bipolar disorder and schizophrenia. We describe completion and analysis of 95.5 megabases (Mb) of sequence from chromosome 13, which contains 633 genes and 296 pseudogenes. We estimate that more than 95.4% of the protein-coding genes of this chromosome have been identified, on the basis of comparison with other vertebrate genome sequences. Additionally, 105 putative non-coding RNA genes were found. Chromosome 13 has one of the lowest gene densities (6.5 genes per Mb) among human chromosomes, and contains a central region of 38 Mb where the gene density drops to only 3.1 genes per Mb.

Objectives/hypothesis: The objective was to reveal the location of the neuromuscular junctions in a three-dimensional reconstruction of the human thyroarytenoid muscle within the true vocal fold., Study Design: Immunohistochemical analysis of serially sectioned human true vocal folds was performed, followed by reconstruction in three dimensions using computer imaging software., Methods: Six fresh human larynges from autopsy were harvested, fixed in formalin, and embedded in paraffin. Eight vocal cords were studied from these six larynges. Five-micron serial sections were collected throughout the entire vocal cord in an axial plane at 500-microm intervals. Immunohistochemical analysis was performed with anti-synaptophysin antibody. A computer-controlled imaging and reconstruction system was used to create a three-dimensional reconstruction from the serial sections and to represent the location of the clustered band of neuromuscular junctions within each true vocal fold. The vocal cord was divided into equal thirds from anterior to posterior for statistical analysis., Results: The most neuromuscular junctions (74%) were located in the middle third, and the least (7%) were found in the anterior third. The difference in anterior-to-posterior distribution was statistically significant in all eight specimens by chi2 analysis (P <.001)., Conclusion: The distribution of neuromuscular junctions is not random within the human thyroarytenoid muscle. Because neuromuscular junctions are most highly concentrated in a band within the mid belly of the muscle, botulinum toxin type A (Botox) injection in patients with spasmodic dysphonia should be targeted to this region.

Chromosome 6 is a metacentric chromosome that constitutes about 6% of the human genome. The finished sequence comprises 166,880,988 base pairs, representing the largest chromosome sequenced so far. The entire sequence has been subjected to high-quality manual annotation, resulting in the evidence-supported identification of 1,557 genes and 633 pseudogenes. Here we report that at least 96% of the protein-coding genes have been identified, as assessed by multi-species comparative sequence analysis, and provide evidence for the presence of further, otherwise unsupported exons/genes. Among these are genes directly implicated in cancer, schizophrenia, autoimmunity and many other diseases. Chromosome 6 harbours the largest transfer RNA gene cluster in the genome; we show that this cluster co-localizes with a region of high transcriptional activity. Within the essential immune loci of the major histocompatibility complex, we find HLA-B to be the most polymorphic gene on chromosome 6 and in the human genome.

Background: Squamous cell carcinoma of the low cervical area may be secondary to stomal recurrence following laryngectomy, low cervical esophageal disease, or peritracheal metastasis. Most often patients with disease in this area have already received both surgery and radiotherapy. Prior to Sisson's description of the trans-sternal radical neck dissection or mediastinal dissection the management and prognosis was uniformly poor. Since then, a number of authors have reported their experience with mediastinal dissection. Survival remains poor but palliation has been acceptable. Unfortunately, resectability of the disease cannot often be determined prior to the actual surgical procedure. A number of patients are explored only to have the procedure terminated. Thoracoscopy is a procedure that involves insertion of two or three trocars into the right thoracic cavity with collapse of the right lung. A form of endoscopic surgery, it permits visualization and dissection of the important structures of the mediastinum. Tracheal, esophageal, and great vessel invasion by tumor can be evaluated., Methods: Prospectively, all patients initially seen with stomal recurrence from 1991 to 1994 were evaluated. CT scans, MRIs as well as thoracoscopy were performed when indicated., Results: One patient required conversion to a minithoracotomy involving a 7-cm chest incision. The patient was found to have unresectable disease with tumor involving the great vessels of the mediastinum. A second patient was found to have unresectable disease with tumor encasing the subclavian artery. The third patient was found to have no mediastinum involvement. The patient with no mediastinum involvement underwent a stomal resection with mediastinal dissection. Reconstruction with a pectoralis major myogenous flap was performed. The patient has remained disease free to date. The remaining two patients were judged to have unresectable disease and were offered palliative treatment. Both of these patients died of the disease within 6 months., Conclusions: Thoracoscopy provides important information in judging the surgical resectability of patients with stomal recurrence. This procedure has not been previously described in the otolaryngologic literature. We provide some suggestions for its use in the evaluation of the mediastinal extent of disease.

Background: Abdominal aortic aneurysm and renal neoplasm are occasionally discovered concurrently. Simultaneous operative therapy may be an effective alternate management strategy to a staged procedure., Patients and Methods: The medical records of 10 consecutive patients undergoing abdominal aortic aneurysm repair and nephrectomy for renal neoplasm were reviewed. Data collected included mode of presentation, preoperative evaluation, renal pathology, and in-hospital morbidity and mortality. Long-term follow-up was obtained through office records and telephone contact., Results: In 7 patients, the renal mass was identified during evaluation of abdominal aortic aneurysm. The aneurysm was identified during evaluation of hematuria in 2 patients. One patient was discovered to have both conditions simultaneously. All patients underwent successful aneurysm repair and nephrectomy. Pathology revealed 6 renal cell carcinomas, 2 complex cysts, 1 hemangiopericytoma, and 1 oncocytoma. Four patients have died in the follow-up period: 1 of metastatic cancer and 3 of unrelated causes. There have been no cases of graft infection., Conclusion: Simultaneous abdominal aortic aneurysm repair and nephrectomy for neoplasm is an appropriate management strategy for selected patients.

We describe our experience with a technique for simultaneous urinary and fecal diversion using a single abdominal stoma. The procedure requires the construction of a diverting loop colostomy with division of the colon approximately 15 cm. distal to the stoma. This distal segment of colon acts as a urinary conduit, and allows internal separation of the urine and fecal streams. The procedure has been used in patients without a prior stoma as well as those with existing loop and end colostomies. Unlike the watery diarrhea associated with the wet colostomy described previously, these patients experience a continuous urine output and intermittent semiformed bowel movements. Complications have been minimal: there have been no episodes of clinical pyelonephritis, no new electrolyte problems and no significant stomal complications. In 1 patient late radiographic evidence of hydronephrosis developed associated with advancing metastatic disease, while in another late bilateral ureterocolonic strictures developed. The majority of patients died of the underlying cancer but 1 died of a myocardial infarction 2 weeks postoperatively. This procedure has now been performed in 11 patients with followup from 0.5 to 80 months. The results are gratifying for a group of highly complex cases.

Prolactin and testosterone are synergistic in stimulating growth of the rat prostate. The lateral lobe is more sensitive to this synergism than the ventral and dorsal lobes. To investigate whether prolactin acts directly in the rat prostate or indirectly through another systemic mediator, anterior pituitary grafts (1 mm3) were implanted in the lateral prostate of castrated Sprague-Dawley rats in whom a 0.5 cm or 1.0 cm testosterone-filled silastic tubing was implanted subcutaneously at the same time. Rats were randomly assigned to receive either the pituitary or a muscle chip of similar size grafted beneath the fascia lateral to the lateral prostate. Twenty-one days later, serum prolactin levels were not elevated in pituitary-grafted animals and were not significantly different from those in muscle-grafted rats. The mean lateral prostate weight on the grafted side in pituitary-implanted rats with 1.0 cm testosterone tubing was 43% heavier than either that of the contralateral side or the corresponding weights in muscle-implanted rats. In pituitary-implanted rats with 0.5 cm testosterone tubing, the mean lateral prostate weight on the grafted side was 60% heavier than either that of the contralateral side or that of the corresponding weights in muscle-implanted rats. The weight of the ventral and dorsal lobes of the prostate was not significantly affected by the presence of pituitary grafts in one of the lateral lobes. The local effect of prolactin on the lateral prostate was further demonstrated by an overall decline in tissue concentrations of dihydrotestosterone in the grafted side. These results provided evidence to indicate that there was a direct effect of prolactin on growth of the lateral prostate in rats.

The effects of potential serum inhibitors upon the growth of calcium hydroxyapatite (HAP) crystals were studied in vivo using a pH-stat system. Whole serum caused a marked decrease in crystal growth in a dose-dependent manner. At a protein concentration of 13 micrograms/ml, whole serum reduced the initial rate of crystal growth from 84 mumol of KOH/h to 48 mumol of KOH/h. Serum components were separated by ultrafiltration (10,000 Da cut-off). The high-molecular-mass fraction containing serum proteins gave an initial rate of crystal growth of 48 mumol of KOH/h compared with 64 mumol of KOH/h given by the low-molecular-mass components. Thus, two-thirds of the inhibitory activity was associated with proteins and other serum macromolecules, whilst the remainder of the activity was associated with the low-molecular-mass components. Albumin-depleted serum showed an initial rate of crystal growth of 59 mumol of KOH/h, whilst albumin purified by affinity chromatography gave an initial rate of crystal growth of 56 mumol of KOH/h at the same protein concentration. Albumin, therefore, not only accounts for half of the protein concentration in serum, but also contributes half of the inhibitory activity of the high-molecular-mass fraction. Heat denaturation of albumin dramatically enhanced the inhibition of HAP seeded growth with the initial rate of crystal growth falling to 27 mumol of KOH/h after treatment compared with 62 mumol of KOH/h before denaturation. Isoelectric focusing indicated that the tertiary and secondary structure, and hence the distribution of surface charge of albumin, are altered by heat denaturation. Gels showed a mixture of species with isoelectric points ranging from 6.0 to 5.0 compared with the native protein value of 4.7. These data suggest that adsorption of serum proteins to the growing HAP crystals is one mechanism of growth inhibition. It is also clear that the most abundant serum protein, albumin, is an important mediator of this process.

Early decatheterization directed by postoperative gravity cystography in 55 consecutive radical prostatectomy patients is described. The catheter-free status was 22 per cent by postoperative day 8, 62 per cent by postoperative day 11 and 80 per cent by postoperative day 14. Cystograms performed beginning on postoperative day 7 identified 3 groups of patients and dictated their management: 1) no extravasation resulting in immediate catheter removal (36 patients), 2) moderate extravasation requiring repeat cystography leading to decatheterization by postoperative day 15 (9 patients) and 3) severe extravasation necessitating prolonged catheter drainage (8 patients). A decatheterization protocol is presented.

The status of the biochemical markers explored for use in patients with carcinoma of the prostate is reviewed. No unique marker has been identified. However, a variety of substances, primarily enzymes and specific proteins, found in the serum, urine, and prostatic fluid, have been evaluated. Their main value remains in the staging of disease and the monitoring of response to therapy.

Since its introduction for general use, the role of rigid ureteroscopy in the diagnosis and therapy of urological disease has been in evolution. We evaluated retrospectively the experience at our institution with rigid ureteroscopy from January 1983 to July 1986 in an attempt to identify clinical situations or techniques that tended to increase the incidence of either success or complications. We determined that ureteroscopic complications were rare in procedures performed for diagnosis compared to those performed for calculi (2 of 33 or 6 per cent versus 27 of 99 or 27 per cent, p less than 0.025). The likelihood of failure or complication was greater for stones above than for those below the pelvic brim (15 of 25 or 60 per cent versus 26 of 75 or 35 per cent, p less than 0.05). Major complications were more common early in our experience (9 of 63 or 14 per cent versus 2 of 69 or 3 per cent for the combined years 1983 and 1984 compared to 1985 and 1986, p less than 0.05). Our success rates in the treatment of calculous disease were similar to those reported previously, and they were somewhat better for stones located below (62 of 75 or 83 per cent) than for those above (17 of 25 or 68 per cent) the pelvic brim. Based on our findings we conclude that carefully performed diagnostic ureteroscopy has little potential for major complications, ureteroscopy for stones above the pelvic brim should be avoided when possible, and an increased rate of complications and failures is expected early in any series owing at least partly to the learning curve effect.

We report on the sonographic (US) and magnetic resonance imaging (MRI) appearance of a mixed sex-cord stromal tumor of the testis. The case is notable due to its rarity, its unusual imaging characteristics as correlated with pathology, and the ability of MRI, in this particular case, to give more complete information than US as to the character of the lesion.

A new technique to achieve simultaneous diversion of the urinary and fecal streams using a single abdominal stoma is described. The procedure consists of the construction of a diverting loop colostomy with division of the colon approximately 10 to 15 cm. distal to the stoma. The segment of colon distal to the stoma, the urine limb, acts as a urinary conduit. To date 3 patients have undergone the procedure with followup of 3, 13 and 18 months. Neither upper tract infection nor upper tract deterioration has occurred. The potential role of this procedure to treat a difficult group of patients is discussed.

The application of secondary-electron capture negative-ion (SECNI) mass spectrometry to the analysis of metal-organic compounds is described and typical examples are discussed. Negative-ion mass spectra are simple, molecular anions and ligand ions being the predominant species. Metallic or ligand impurities are readily identified by this technique, which makes it extremely useful for the determination of purity and formulation of metal-organic compounds. Because of its sensitivity, the technique is also valuable for trace metal analysis.

The gene for the Eco RV methylase has been cloned into a plasmid under control of the strong lambda PL promoter and overexpressed in E. coli. This plasmid, pVIC1, gives reliable overexpression of the methylase at levels of about 20% of total protein. Maximum yields of soluble protein are achieved after about 6 hours of induction. If the cells are harvested later than this much of the enzyme is found in the pellet fraction following centrifugation. A two column purification scheme using phosphocellulose and Blue-Sepharose chromatography has been developed. This yielded pure methylase in amounts of 5mg per gram E. coli cell paste. The enzyme is monomeric and methylates the first deoxyadenosine residue in its recognition sequence GATATC.

Frequency and distribution of atypical prostatic hyperplasia were assessed in 51 total prostatectomy specimens for cancer and the data were compared to similar data obtained from analysis of 51 autopsy specimens. Enlargement of columnar cell nuclei in conjunction with preservation of basal cells was chosen as the only criterion for atypia. Depending on the degree of nuclear enlargement, atypia was divided into mild and severe degrees. The evaluation of nuclear atypia was applied to areas of carcinoma as well as to atypical prostatic hyperplasia. There were 3 major findings. 1) Atypical prostatic hyperplasia was found more frequently in prostatectomy specimens (48 of 51 cases) than in autopsy specimens (14 of 37 cases after exclusion of cancer-associated cases) and the difference was significant (p less than 0.001). In addition, atypical prostatic hyperplasia found in prostatectomy specimens was more frequently of severe degree than that in the autopsy specimens (42 of 48 versus 3 of 14 cases, p less than 0.001). 2) The distribution of atypical prostatic hyperplasia and carcinoma in prostatectomy specimens was similar. 3) In a majority of prostatectomy specimens atypical prostatic hyperplasia, when found, was located at sites separate from carcinoma as well as in contiguous areas. Based on these data it is suggested that the presence of a severe degree of nuclear atypia in specimens removed for benign conditions or in prostatic needle biopsies may signify an increased incidence of coexisting carcinoma elsewhere in the prostate or of carcinoma developing in the future. Close followup of these patients may be indicated.

Twenty patients with adenocarcinoma of the prostate underwent postradical prostatectomy adjuvant external beam megavoltage radiation therapy because of periprostatic disease in histologic evaluation of the resected specimen. Fourteen of these patients had pathologic Stage C and 6 pathologic Stage D1 disease. Treatment in most patients consisted of 5,000 rad delivered to the true pelvis. The five-year recurrence-free survival was 75 per cent for pathologic Stage C and 41 per cent for Stage D1 disease. The median time to first evidence of treatment failure was fifty months for D1 patients and has not been reached by the C group. Minor complications occurred in 85 per cent of patients and major complications in 5 per cent. In 1 patient with mild, postoperative stress incontinence total urinary incontinence developed after radiation therapy. These preliminary observations suggest a prolonged disease-free interval with an acceptable morbidity is obtained utilizing this regimen.

We report a case of a granulosa cell tumor of the testis. The ultrastructural characteristics of this rare tumor were compared to its homologue in the ovary and they were similar.

We reviewed the tissue histology of 115 patients with clinically localized carcinoma to determine the correlation between tumor grades in the biopsy and the prostatectomy specimen. Gleason's primary and secondary pattern score systems were used, and each specimen was graded on a scale of 2 to 10 by a referee pathologist in a blind fashion. If the difference in the summed primary and secondary grades in the 2 specimens was no more than 1 grade, the discrepancy was regarded as insignificant. In all but 32 cases initial diagnostic biopsy specimens predicted accurately the final prostatectomy specimen score. The discrepancy was 3 grades in 7 cases and 2 grades in 25 cases. As a result, the lesions in 19 cases were changed from a well differentiated (2 to 4), a moderately differentiated (5 to 7) or a poorly differentiated (8 to 10) lesion to another of these categories. The lesions were upgraded from a well differentiated to a moderately differentiated category in 9 cases and from a moderately to a poorly differentiated category in 4 cases. The lesions were downgraded from a moderately differentiated to a well differentiated category in 6 cases. In 13 other cases the discrepancy was 2 but the lesion remained within the moderately differentiated group. Although in 19 cases the cancerous tissue occupied less than 10 per cent of the biopsy specimen, accurate prediction could be made in 16. The results indicate that diagnostic biopsy specimens will predict the grade of the primary tumor in a majority (72 per cent) but not all of the cases.