Diversity in the germline antibody repertoire. Molecular evolution of the T15 VN gene family.

The T15 heavy chain variable region (VH) gene family in BALB/c mice includes four elements each greater than 88% homologous with the other. One of these elements, V1, encodes virtually all of the VH regions in BALB/c antiphosphorylcholine antibodies, while another element, V3, is a pseudogene and cannot be transcribed or translated. We have examined the structural features of this VH gene family in other mouse strains and, in particular, have cloned and sequenced the alleles of these gene segments present in B10.P mice. Each of the four B10.P sequences can be matched with its allelic counterpart in BALB/c mice. This represents the first successful analysis of allelism in antibody variable region gene segments. The V1B10.P allele, like its BALB/c counterpart, encodes most of the known phosphorylcholine binding heavy chains from C37BL/6 mice. Similarly, the V3B10.P gene segment is a pseudogene like V3BALB, although only two of four abnormalities present in the BALB/c allele are also present in the B10.P allele. Careful analysis of the specific substitutions observed in the T15 VH gene family suggests that environmental selection for functional combining regions contributes significantly to the pattern of variation in the germline antibody repertoire. In addition, evidence is presented supporting frequent gene conversion events in the divergence of antibody genes.

Phosphate-binding specificities of monoclonal antibodies against phosphoinositides in liposomes.

Monoclonal antibodies against phosphatidylinositol phosphate were produced after injecting a mouse with liposomes containing dimyristoylphosphatidylcholine, cholesterol, phosphatidylinositol phosphate and lipid A. The antibodies raised were IgM (kappa) and their activities were assayed by complement-dependent damage to liposomes lacking lipid A but containing the rest of original immunizing mixture of lipids. Three of the four antibodies selected cross-reacted with liposomes containing phosphatidylinositol instead of phosphatidylinositol phosphate; and two of the antibodies cross-reacted with liposomes containing phosphatidylinositol diphosphate. Each of the antibodies had a phosphate-binding specificity. Each also cross-reacted with liposomes containing sulfogalactosyl ceramide, but not with liposomes containing galactosyl ceramide, or gangliosides or with liposomes containing lipid A but lacking phosphoinositides. Recognition of sulfogalactosyl ceramide probably occurred because the chemical characteristics of the sulfate group were sufficiently similar to those of phosphate to allow recognition by the antibody. The phosphate-binding specificity was further confirmed by inhibition by phosphocholine, inositol hexaphosphate, ATP, AMP and even sodium phosphate, but not by choline or inositol.

Vasopressin-induced antinociception: an investigation into its physiological and hormonal basis.

Systemically administered lysine-8-vasopressin (LVP; 16-128 micrograms/kg) was found to induce a potent and dose-dependent antinociceptive effect, as measured by the tail-flick test in the rat. This effect could be seen in the absence of any significant change in general activity, indicating that it was not due to sedation or general motor debilitation. The antinociceptive effect of LVP does not appear to be mediated by endogenous opiates or other pituitary hormones, as evidenced by: 1) the lack of antagonism by the opiate receptor blocker naloxone, 2) the lack of cross-tolerance with morphine, and 3) its persistence after hypophysectomy. Des-glycinamide-LVP, a vasopressin analog with no appreciable pressor or antidiuretic action, showed no antinociceptive activity (128 micrograms/kg), and des-amino-arginine-vasopressin, a vasopressin analog with minimal pressor activity but greatly enhanced antidiuretic activity, was also relatively ineffective (128 micrograms/kg). These results suggest that the antinociceptive activity of vasopressin may be related to receptor types similar to those mediating its pressor effects. Nevertheless, the antinociceptive action of vasopressin does not appear to be secondary to its pressor activity, since phenylephrine failed to induce an antinociceptive effect at a dosage that mimicked the pressor response to vasopressin. These results are in concert with a growing body of evidence suggesting that vasopressin may be one of several nonopiate peptides that play a role in the modulation of pain sensitivity.

An automated instrument for the performance of enzymatic DNA sequencing reactions.

An instrument has been developed for the automation of enzymatic DNA sequencing reactions. Up to 96 DNA templates contained in a microtiter plate can be processed for either radioactive or fluorescence-based sequence analysis in a three-hour period. The quality of the resultant data is comparable to that obtained manually. The system is simple, flexible and is readily adapted to the use of new polymerases or modified experimental protocols.

Tuberculous abscess of the pancreas in AIDS: CT findings.

Tuberculous abscess of the pancreas is a rare complication of disseminated tuberculosis. The computed tomographic appearance of a tuberculous pancreatic abscess in a patient with acquired immune deficiency syndrome (AIDS) is described. One should consider this diagnosis whenever a patient with AIDS has diffuse abdominal lymphadenopathy.

Discoid medial meniscus: two cases of tears presenting as locked knee due to athletic trauma.

Two patients with a rare, massive type of discoid medial meniscus have been described. Both presented with a locked knee due to athletic trauma in the third and fifth decade of life, respectively. Clinically, discoid meniscus has only nonspecific signs. The arthrogram has proved to be a helpful preoperative diagnostic tool. Definitive diagnosis and treatment can be made with arthroscopy.

Injuries to runners: a study of entrants to a 10,000 meter race.

As the number of runners has increased dramatically, so has the incidence of running-related injuries. In order to determine what training factors are associated with running-related injuries, as well as what percentage of injured runners seeks professional medical attention, a random sample of entrants to a 10 kilometer race was asked to complete a questionnaire. There were 451 respondents, 355 men and 96 women, with a nonresponse rate of 12.7%. Nonrespondents did not differ from respondents with regard to age or sex. Forty-seven percent of respondents indicated that they had sustained a running-related injury in the last 2 years. Injured runners differed significantly from noninjured runners in that they were more likely to have run more miles per week, run more days per week, run a faster pace, run more races in the last year, stretched before running, and not participated regularly in other sports. Associated with injury, but not statistically significant, were those who had run marathons and had done muscle-strengthening exercises. No association was found with regard to the length of time running, running surfaces, part of the foot first contacting the ground, or running intervals, sprints, or hills. Seventy percent of those injured sought professional medical care, with 76% of these having a good or excellent recovery from their injuries. Compliance with medical advice correlated well with treatment success.

An epidemiologic study of squash injuries.

A retrospective investigation of squash-related injuries incurred at a private and a public club in New York was undertaken to gain insight into the incidence and nature of such injuries. Telephone interviews were conducted with 200 randomly selected individuals to obtain their entire injury history. Sixty-nine of the 155 squash players contacted sustained injuries during their participation. Some had multiple injuries. This resulted in an overall injury rate of 44.5%. Strains and sprains accounted for over one-third of the injuries. Nearly one-half of the injuries involved the lower extremity, with the ankle and lower leg being injured most often. Forty-seven percent of the injuries seen were considered disabling because the patients were out of action for more than two weeks after injury. Players over the age of 40 are at increased risk for injury, as are newcomers to the game. Increased injury rates were also associated with an increased frequency of play among females. Only rarely will an injured squash player become permanently impaired.

Imaging of degenerative brain disorders.

Recent advances have been made in defining the imaging findings associated with degenerative brain disorders, especially Alzheimer's disease, multi-infarct dementia, and multiple sclerosis. CT and MR imaging are capable of evaluating structural changes seen in these abnormalities. Positron emission tomography and single-photon emission CT studies, by evaluating metabolic changes, may demonstrate abnormalities before those seen on CT or MR imaging. Recent articles pertaining to the imaging of degenerative brain disorders are reviewed and discussed.

Traumatic "windblown knees": case report of bilateral knee ligament rupture of the opposite compartment of contralateral knees.

An unusual case of rupture of the medial and posterior ligaments of the left knee, and lateral ligaments of the right knee, due to a direct vehicular blow is reported. Surgical repair of the left knee and conservative treatment of the right (lateral ligaments) gave excellent results. The types of lesions produced on each knee could almost be predicted by the sites of skin abrasions.

Human fibroblast interferon in treatment of viral diseases of the skin and mucous membranes.

The therapeutic effect of human fibroblast interferon (HFIF) was studied in 33 patients. Seven had ophthalmic lesions (three due to adenovirus Type 8, four to herpes simplex virus, and one to herpes zoster) and were treated with HFIF. In the four patients with herpes simplex keratitis, HFIF was given in addition to standard therapy or together with other antiviral agents. Ten other patients, 8 with herpes simplex or herpes zoster skin or mucous membrane lesions, were treated with HFIF. HFIF was incorporated into an ointment as well as into a solution for subconjunctival infections. Although the number of cases was small, our results showed that HFIF was effective in shortening the course of the disease.

Acromioclavicular dislocations: treatment by transfer of the conjoined tendon and distal end of the coracoid process to the clavicle.

A retrospective study of 23 acute and 6 chronic acromioclavicular dislocations treated by surgical transfer of the distal 1/2 inch of the coracoid process with the attached conjoined tendon of the coracobrachialis and short head of the biceps to the clavicle revealed 14 excellent, 14 good and one fair result. Results were determined according to symptoms, range of motion at the shoulder and elbow, strength, anatomic reduction, and return to previous activities. Although most patients with this injury are treated conservatively, this procedure is reserved for the athlete or manual laborer below age 45 years, especially with involvement of the dominant-extremity. The 29 cases were evaluated 20--108 months following surgery. Thirteen additional cases with less than 18 month follow-up have also been good or excellent. Weakness and pain have not been as pronounced following this procedure in vigorous individuals as have been noted after conservative treatment. Few postoperative complications developed, and early return to competitive athletics was possible.